Skip to main content

Advertisement

SpringerLink
Log in

Promise of adeno-associated virus as a gene therapy vector for cardiovascular diseases

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

Cardiovascular diseases pose a unique threat to global mortality because it presents as one of the most diverse conglomerations of pathophysiological conditions that can create significant casualty even without straying into its collateral damage. This puts them right beside obesity and cancer in terms of severity. Their pervasive nature and high prevalence prompted biologists to seek newer prophylactic avenues of addressing this global hazard, among which adeno-associated virus (AAV) gene therapy rose to significant prominence. By virtue of its unrivaled clinical safety quotient, AAVs have been used to rectify various subtypes of cardiovascular ailments, beginning from commonly occurring heart failure to vascular diseases. The review focuses on the history of AAV-mediated gene therapy and contemporary breakthroughs in terms of novel innovations in vector engineering to reduce detargeting, immune response, untimely expression, and so on. We have also focused on the molecular world of cardiomyocytes and endothelial cells but interpreted the therapies in a broader context of cardiovascular pathology. The advances made in each mode of intervention as well as the ones that are beyond the scope of AAV gene therapy or has not been approached through AAV gene therapy as of now have been provided in detail to illustrate the bigger picture of where we stand to combat cardiovascular diseases most efficiently.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Murray CJ, Lopez AD (1997) Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet 349(9061):1269–1276. doi:10.1016/S0140-6736(96)07493-4

    Article  CAS  PubMed  Google Scholar 

  2. Murray CJ, Lopez AD (1997) Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 349(9063):1436–1442. doi:10.1016/S0140-6736(96)07495-8

    Article  CAS  PubMed  Google Scholar 

  3. Reddy KS (2004) Cardiovascular disease in non-Western countries. N Engl J Med 350(24):2438–2440

    Article  CAS  PubMed  Google Scholar 

  4. Moran AE, Forouzanfar MH, Roth GA, Mensah GA, Ezzati M, Flaxman A, Murray CJ, Naghavi M (2014) The global burden of ischemic heart disease in 1990 and 2010: the Global Burden of Disease 2010 study. Circulation 129(14):1493–1501. doi:10.1161/CIRCULATIONAHA.113.004046

    Article  PubMed  PubMed Central  Google Scholar 

  5. Bennett DA, Krishnamurthi RV, Barker-Collo S, Forouzanfar MH, Naghavi M, Connor M, Lawes CM, Moran AE, Anderson LM, Roth GA, Mensah GA, Ezzati M, Murray CJ, Feigin VL (2014) The global burden of ischemic stroke: findings of the GBD 2010 study. Glob Heart 9(1):107–112. doi:10.1016/j.gheart.2014.01.001

    Article  PubMed  Google Scholar 

  6. Krishnamurthi RV, Feigin VL, Forouzanfar MH, Mensah GA, Connor M, Bennett DA, Moran AE, Sacco RL, Anderson LM, Truelsen T, O'Donnell M, Venketasubramanian N, Barker-Collo S, Lawes CM, Wang W, Shinohara Y, Witt E, Ezzati M, Naghavi M, Murray C (2013) Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet Glob Health 1(5):e259–e281. doi:10.1016/S2214-109X(13)70089-5

    Article  PubMed  PubMed Central  Google Scholar 

  7. Krishnamurthi RV, Moran AE, Forouzanfar MH, Bennett DA, Mensah GA, Lawes CMM, Barker-Collo S, Connor M, Roth GA, Sacco R (2014) The global burden of hemorrhagic stroke: a summary of findings from the GBD 2010 study. Glob Heart 9(1):101–106

    Article  PubMed  Google Scholar 

  8. Feigin VL, Forouzanfar MH, Krishnamurthi R, Mensah GA, Connor M, Bennett DA, Moran AE, Sacco RL, Anderson L, Truelsen T (2014) Global and regional burden of stroke during 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet 383(9913):245–255

    Article  PubMed  PubMed Central  Google Scholar 

  9. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L (2004) Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 364(9438):937–952. doi:10.1016/S0140-6736(04)17018-9

    Article  PubMed  Google Scholar 

  10. Rosengren A, Hawken S, Ounpuu S, Sliwa K, Zubaid M, Almahmeed WA, Blackett KN, Sitthi-amorn C, Sato H, Yusuf S (2004) Association of psychosocial risk factors with risk of acute myocardial infarction in 11119 cases and 13648 controls from 52 countries (the INTERHEART study): case-control study. Lancet 364(9438):953–962. doi:10.1016/S0140-6736(04)17019-0

    Article  PubMed  Google Scholar 

  11. Vamadevan AS, Prabhakaran D (2010) Coronary heart disease in Indians: implications of the INTERHEART study. Indian J Med Res 132(5):561

    Google Scholar 

  12. Anand SS, Islam S, Rosengren A, Franzosi MG, Steyn K, Yusufali AH, Keltai M, Diaz R, Rangarajan S, Yusuf S (2008) Risk factors for myocardial infarction in women and men: insights from the INTERHEART study. Eur Heart J 29(7):932–940

    Article  PubMed  Google Scholar 

  13. Braunwald E (2014) The war against heart failure: the Lancet lecture. Lancet 385(9970):812–824. doi:10.1016/S0140-6736(14)61889-4

    Article  PubMed  Google Scholar 

  14. Setsuta K, Seino Y, Ogawa T, Ohtsuka T, Seimiya K, Takano T (2004) Ongoing myocardial damage in chronic heart failure is related to activated tumor necrosis factor and Fas/Fas ligand system. Circ J 68(8):747–750

    Article  CAS  PubMed  Google Scholar 

  15. Kutsuzawa D, Arimoto T, Watanabe T, Shishido T, Miyamoto T, Miyashita T, Takahashi H, Niizeki T, Takeishi Y, Kubota I (2012) Ongoing myocardial damage in patients with heart failure and preserved ejection fraction. J Cardiol 60(6):454–461

    Article  PubMed  Google Scholar 

  16. Velagaleti RS, Pencina MJ, Murabito JM, Wang TJ, Parikh NI, D'Agostino RB, Levy D, Kannel WB, Vasan RS (2008) Long-term trends in the incidence of heart failure after myocardial infarction. Circulation 118(20):2057–2062

    Article  PubMed  PubMed Central  Google Scholar 

  17. Jhund PS, McMurray JJV (2008) Heart failure after acute myocardial infarction a lost battle in the war on heart failure? Circulation 118(20):2019–2021

    Article  PubMed  Google Scholar 

  18. Hellermann JP, Jacobsen SJ, Redfield MM, Reeder GS, Weston SA, Roger VL (2005) Heart failure after myocardial infarction: clinical presentation and survival. Eur J Heart Fail 7(1):119–125

    Article  PubMed  Google Scholar 

  19. McAlister FA, Quan H, Fong A, Jin Y, Cujec B, Johnson D (2008) Effect of invasive coronary revascularization in acute myocardial infarction on subsequent death rate and frequency of chronic heart failure. Am J Cardiol 102(1):1–5

    Article  PubMed  Google Scholar 

  20. Verma IM, Somia N (1997) Gene therapy-promises, problems and prospects. Nature 389(6648):239–242

    Article  CAS  PubMed  Google Scholar 

  21. Somia N, Verma IM (2000) Gene therapy: trials and tribulations. Nat Rev Genet 1(2):91–99

    Article  CAS  PubMed  Google Scholar 

  22. Scollay R (2001) Gene therapy. Ann N Y Acad Sci 953(1):26–30

    Article  CAS  PubMed  Google Scholar 

  23. Hoggan MD, Blacklow NR, Rowe WP (1966) Studies of small DNA viruses found in various adenovirus preparations: physical, biological, and immunological characteristics. Proc Natl Acad Sci 55(6):1467–1474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Atchison RW, Casto BC, Hammon WM (1965) Adenovirus-associated defective virus particles. Science 149(3685):754–755

    Article  CAS  PubMed  Google Scholar 

  25. Berns KI, Bohenzky RA (1987) Adeno-associated viruses: an update. Adv Virus Res 32:243–306

    Article  CAS  PubMed  Google Scholar 

  26. Siegl G, Bates RC, Berns KI, Carter BJ, Kelly DC, Kurstak E, Tattersall P (1985) Characteristics and taxonomy of Parvoviridae. Intervirology 23(2):61–73

    Article  CAS  PubMed  Google Scholar 

  27. Thomas CE, Ehrhardt A, Kay MA (2003) Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genet 4(5):346–358

    Article  CAS  PubMed  Google Scholar 

  28. Daya S, Berns KI (2008) Gene therapy using adeno-associated virus vectors. Clin Microbiol Rev 21(4):583–593. doi:10.1128/cmr.00008-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Maeda Y, Ikeda U, Ogasawara Y, Urabe M, Takizawa T, Saito T, Colosi P, Kurtzman G, Shimada K, Ozawa K (1997) Gene transfer into vascular cells using adeno-associated virus (AAV) vectors. Cardiovasc Res 35(3):514–521. doi:10.1016/s0008-6363(97)00163-6

    Article  CAS  PubMed  Google Scholar 

  30. Richter M, Iwata A, Nyhuis J, Nitta Y, Miller AD, Halbert CL, Allen MD (2000) Adeno-associated virus vector transduction of vascular smooth muscle cells in vivo. Physiol Genomics 2(3):117–127

    CAS  PubMed  Google Scholar 

  31. Melo LG, Agrawal R, Zhang L, Rezvani M, Mangi AA, Ehsan A, Griese DP, Dell’Acqua G, Mann MJ, Oyama J, Yet S-F, Layne MD, Perrella MA, Dzau VJ (2002) Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene. Circulation 105(5):602–607. doi:10.1161/hc0502.103363

    Article  CAS  PubMed  Google Scholar 

  32. Nicklin SA, Buening H, Dishart KL, De Alwis M, Girod A, Hacker U, Thrasher AJ, Ali RR, Hallek M, Baker AH (2001) Efficient and selective AAV2-mediated gene transfer directed to human vascular endothelial cells. Mol Ther 4(3):174

    Article  CAS  PubMed  Google Scholar 

  33. Pajusola K, Gruchala M, Joch H, Lüscher TF, Ylä-Herttuala S, Büeler H (2002) Cell-type-specific characteristics modulate the transduction efficiency of adeno-associated virus type 2 and restrain infection of endothelial cells. J Virol 76(22):11530–11540. doi:10.1128/jvi.76.22.11530-11540.2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Zincarelli C, Soltys S, Rengo G, Rabinowitz JE (2008) Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection. Mol Ther 16(6):1073–1080

    Article  CAS  PubMed  Google Scholar 

  35. Zincarelli C, Soltys S, Rengo G, Koch WJ, Rabinowitz JE (2010) Comparative cardiac gene delivery of adeno-associated virus serotypes 1-9 reveals that AAV6 mediates the most efficient transduction in mouse heart. Clinical and translational science 3(3):81–89. doi:10.1111/j.1752-8062.2010.00190.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gregorevic P, Blankinship MJ, Allen JM, Crawford RW, Meuse L, Miller DG, Russell DW, Chamberlain JS (2004) Systemic delivery of genes to striated muscles using adeno-associated viral vectors. Nat Med 10(8):828–834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Muller OJ, Leuchs B, Pleger ST, Grimm D, Franz W-M, Katus HA, Kleinschmidt JA (2006) Improved cardiac gene transfer by transcriptional and transductional targeting of adeno-associated viral vectors. Cardiovasc Res 70(1):70

    Article  PubMed  CAS  Google Scholar 

  38. Wang Z, Zhu T, Qiao C, Zhou L, Wang B, Zhang J, Chen C, Li J, Xiao X (2005) Adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart. Nat Biotech 23(3):321–328

    Article  CAS  Google Scholar 

  39. Su H, Huang Y, Takagawa J, Barcena A, Arakawa-Hoyt J, Ye J, Grossman W, Kan YW (2006) AAV serotype-1 mediates early onset of gene expression in mouse hearts and results in better therapeutic effect. Gene Ther 13(21):1495–1502

    Article  CAS  PubMed  Google Scholar 

  40. Inagaki K, Fuess S, Storm TA, Gibson GA, McTiernan CF, Kay MA, Nakai H (2006) Robust systemic transduction with AAV9 vectors in mice: efficient global cardiac gene transfer superior to that of AAV8. Mol Ther 14(1):45–53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Pacak CA, Mah CS, Thattaliyath BD, Conlon TJ, Lewis MA, Cloutier DE, Zolotukhin I, Tarantal AF, Byrne BJ (2006) Recombinant adeno-associated virus serotype 9 leads to preferential cardiac transduction in vivo. Circ Res 99(4):e3–e9. doi:10.1161/01.RES.0000237661.18885.f6

    Article  CAS  PubMed  Google Scholar 

  42. Miyagi N, Rao VP, Ricci D, Du Z, Byrne GW, Bailey KR, Nakai H, Russell SJ, McGregor CGA (2008) Efficient and durable gene transfer to transplanted heart using adeno-associated virus 9 vector. The Journal of Heart and Lung Transplantation 27(5):554–560

    Article  PubMed  PubMed Central  Google Scholar 

  43. Vandendriessche T, Thorrez L, Acosta-Sanchez A, Petrus I, Wang L, Ma L, De Waele L, Iwasaki Y, Gillijns V, Wilson JM (2007) Efficacy and safety of adeno-associated viral vectors based on serotype 8 and 9 vs. lentiviral vectors for hemophilia B gene therapy. J Thromb Haemost 5(1):16–24

    Article  CAS  PubMed  Google Scholar 

  44. Bish LT, Morine K, Sleeper MM, Sanmiguel J, Wu D, Gao G, Wilson JM, Sweeney HL (2008) Adeno-associated virus (AAV) serotype 9 provides global cardiac gene transfer superior to AAV1, AAV6, AAV7, and AAV8 in the mouse and rat. Hum Gene Ther 19(12):1359–1368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Yang L, Jiang J, Drouin LM, Agbandje-Mckenna M, Chen C, Qiao C, Pu D, Hu X, Wang D-Z, Li J (2009) A myocardium tropic adeno-associated virus (AAV) evolved by DNA shuffling and in vivo selection. Proc Natl Acad Sci 106(10):3946–3951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. White SJ, Nicklin SA, Büning H, Brosnan MJ, Leike K, Papadakis ED, Hallek M, Baker AH (2004) Targeted gene delivery to vascular tissue in vivo by tropism-modified adeno-associated virus vectors. Circulation 109(4):513–519

    Article  CAS  PubMed  Google Scholar 

  47. White K, Büning H, Kritz A, Janicki H, McVey J, Perabo L, Murphy G, Odenthal M, Work LM, Hallek M (2008) Engineering adeno-associated virus 2 vectors for targeted gene delivery to atherosclerotic lesions. Gene Ther 15(6):443–451

    Article  CAS  PubMed  Google Scholar 

  48. Denby L, Nicklin SA, Baker AH (2005) Adeno-associated virus (AAV)-7 and -8 poorly transduce vascular endothelial cells and are sensitive to proteasomal degradation. Gene Ther 12(20):1534–1538

    Article  CAS  PubMed  Google Scholar 

  49. Zaiss AK, Muruve DA (2005) Immune responses to adeno-associated virus vectors. Current gene therapy 5(3):323–331

    Article  CAS  PubMed  Google Scholar 

  50. Calcedo R, Morizono H, Wang L, McCarter R, He J, Jones D, Batshaw ML, Wilson JM (2011) Adeno-associated virus antibody profiles in newborns, children and adolescents. Clin Vaccine Immunol CVI:05107–05111

    Google Scholar 

  51. Erles K, Sebökovà P, Schlehofer R Jr (1999) Update on the prevalence of serum antibodies (IgG and IgM) to adeno-associated virus (AAV). J Med Virol 59(3):406–411

    Article  CAS  PubMed  Google Scholar 

  52. Li C, Narkbunnam N, Samulski RJ, Asokan A, Hu G, Jacobson LJ, Manco-Johnson MJ, Monahan PE (2012) Neutralizing antibodies against adeno-associated virus examined prospectively in pediatric patients with hemophilia. Gene Ther 19(3):288–294

    Article  CAS  PubMed  Google Scholar 

  53. Brantly ML, Chulay JD, Wang L, Mueller C, Humphries M, Spencer LT, Rouhani F, Conlon TJ, Calcedo R, Betts MR, Spencer C, Byrne BJ, Wilson JM, Flotte TR (2009) Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy. Proc Natl Acad Sci 106(38):16363–16368. doi:10.1073/pnas.0904514106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Stone D, Liu Y, Li Z-Y, Strauss R, Finn EE, Allen JM, Chamberlain JS, Lieber A (2008) Biodistribution and safety profile of recombinant adeno-associated virus serotype 6 vectors following intravenous delivery. J Virol 82(15):7711–7715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Nathwani AC, Davidoff AM, Hanawa H, Hu Y, Hoffer FA, Nikanorov A, Slaughter C, Ng CYC, Zhou J, Lozier JN (2002) Sustained high-level expression of human factor IX (hFIX) after liver-targeted delivery of recombinant adeno-associated virus encoding the hFIX gene in rhesus macaques. Blood 100(5):1662–1669

    Article  CAS  PubMed  Google Scholar 

  56. Ponnazhagan S, Mukherjee P, Yoder MC, Wang X-S, Zhou SZ, Kaplan J, Wadsworth S, Srivastava A (1997) Adeno-associated virus 2-mediated gene transfer in vivo: organ-tropism and expression of transduced sequences in mice. Gene 190(1):203–210

    Article  CAS  PubMed  Google Scholar 

  57. Chirmule N, Propert KJ, Magosin SA, Qian Y, Qian R, Wilson JM (1999) Immune responses to adenovirus and adeno-associated virus in humans. Gene Ther 6(9):1574–1583

    Article  CAS  PubMed  Google Scholar 

  58. Manno CS, Arruda VR, Pierce GF, Glader B, Ragni M, Rasko J, Ozelo MC, Hoots K, Blatt P, Konkle B, Dake M, Kaye R, Razavi M, Zajko A, Zehnder J, Nakai H, Chew A, Leonard D, Wright JF, Lessard RR, Sommer JM, Tigges M, Sabatino D, Luk A, Jiang H, Mingozzi F, Couto L, Ertl HC, High KA, Kay MA (2006) Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med 12(3):342–347

    Article  CAS  PubMed  Google Scholar 

  59. Madsen D, Cantwell ER, O’Brien T, Johnson PA, Mahon BP (2009) Adeno-associated virus serotype 2 induces cell-mediated immune responses directed against multiple epitopes of the capsid protein VP1. J Gen Virol 90(11):2622–2633. doi:10.1099/vir.0.014175-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Sabatino DE, Mingozzi F, Hui DJ, Chen H, Colosi P, Ertl HCJ, High KA (2005) Identification of mouse AAV capsid-specific CD8+ T cell epitopes. Mol Ther 12(6):1023–1033

    Article  CAS  PubMed  Google Scholar 

  61. McTiernan CF, Mathier MA, Zhu X, Xiao X, Klein E, Swan CH, Mehdi H, Gibson G, Trichel AM, Glorioso JC (2007) Myocarditis following adeno-associated viral gene expression of human soluble TNF receptor (TNFRII-Fc) in baboon hearts. Gene Ther 14(23):1613–1622

    Article  CAS  PubMed  Google Scholar 

  62. Gao G, Wang Q, Calcedo R, Mays L, Bell P, Wang L, Vandenberghe LH, Grant R, Sanmiguel J, Furth EE (2009) Adeno-associated virus-mediated gene transfer to nonhuman primate liver can elicit destructive transgene-specific T cell responses. Hum Gene Ther 20(9):930–942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Pober JS, Sessa WC (2007) Evolving functions of endothelial cells in inflammation. Nat Rev Immunol 7(10):803–815

    Article  CAS  PubMed  Google Scholar 

  64. Gao G-P, Alvira MR, Wang L, Calcedo R, Johnston J, Wilson JM (2002) Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc Natl Acad Sci 99(18):11854–11859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Grimm D, Lee JS, Wang L, Desai T, Akache B, Storm TA, Kay MA (2008) In vitro and in vivo gene therapy vector evolution via multispecies interbreeding and retargeting of adeno-associated viruses. J Virol 82(12):5887–5911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Asokan A, Conway JC, Phillips JL, Li C, Hegge J, Sinnott R, Yadav S, DiPrimio N, Nam H-J, Agbandje-McKenna M (2010) Reengineering a receptor footprint of adeno-associated virus enables selective and systemic gene transfer to muscle. Nat Biotechnol 28(1):79–82

    Article  CAS  PubMed  Google Scholar 

  67. Maheshri N, Koerber JT, Kaspar BK, Schaffer DV (2006) Directed evolution of adeno-associated virus yields enhanced gene delivery vectors. Nat Biotechnol 24(2):198–204

    Article  CAS  PubMed  Google Scholar 

  68. Arruda VR, Xiao W (2007) It's all about the clothing: capsid domination in the adeno-associated viral vector world. J Thromb Haemost 5(1):12–15

    Article  CAS  PubMed  Google Scholar 

  69. Hernandez YJ, Wang J, Kearns WG, Loiler S, Poirier A, Flotte TR (1999) Latent adeno-associated virus infection elicits humoral but not cell-mediated immune responses in a nonhuman primate model. J Virol 73(10):8549–8558

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Jaski BE, Jessup ML, Mancini DM, Cappola TP, Pauly DF, Greenberg B, Borow K, Dittrich H, Zsebo KM, Hajjar RJ (2009) Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID trial), a first-in-human phase 1/2 clinical trial. J Card Fail 15(3):171–181. doi:10.1016/j.cardfail.2009.01.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Boutin S, Monteilhet V, Veron P, Leborgne C, Benveniste O, Montus MFO, Masurier C (2010) Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors. Hum Gene Ther 21(6):704–712

    Article  CAS  PubMed  Google Scholar 

  72. Mingozzi F, Chen Y, Edmonson SC, Zhou S, Thurlings RM, Tak PP, High KA, Vervoordeldonk MJ (2013) Prevalence and pharmacological modulation of humoral immunity to AAV vectors in gene transfer to synovial tissue. Gene Ther 20(4):417–424

    Article  CAS  PubMed  Google Scholar 

  73. Calcedo R, Vandenberghe LH, Gao G, Lin J, Wilson JM (2009) Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses. J Infect Dis 199(3):381–390

    Article  PubMed  Google Scholar 

  74. Hui DJ, Basner-Tschakarjan E, Chen Y, Davidson RJ, Buchlis G, Yazicioglu M, Pien GC, Finn JD, Haurigot V, Tai A (2013) Modulation of CD8+ T cell responses to AAV vectors with IgG-derived MHC class II epitopes. Mol Ther 21 (9)

  75. Li C, Diprimio N, Bowles DE, Hirsch ML, Monahan PE, Asokan A, Rabinowitz J, Agbandje-McKenna M, Samulski RJ (2012) Single amino acid modification of adeno-associated virus capsid changes transduction and humoral immune profiles. J Virol 86(15):7752–7759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Sen D, Balakrishnan B, Gabriel N, Agrawal P, Roshini V, Samuel R, Srivastava A, Jayandharan GR (2013) Improved adeno-associated virus (AAV) serotype 1 and 5 vectors for gene therapy. Sci Rep 3:1832. doi:10.1038/srep01832

    Article  PubMed  CAS  Google Scholar 

  77. Sen D, Gadkari RA, Sudha G, Gabriel N, Kumar YS, Selot R, Samuel R, Rajalingam S, Ramya V, Nair SC, Srinivasan N, Srivastava A, Jayandharan GR (2013) Targeted modifications in adeno-associated virus serotype 8 capsid improves its hepatic gene transfer efficiency in vivo. Hum Gene Ther Methods 24(2):104–116. doi:10.1089/hgtb.2012.195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Gabriel N, Hareendran S, Sen D, Gadkari RA, Sudha G, Selot R, Hussain M, Dhaksnamoorthy R, Samuel R, Srinivasan N, Srivastava A, Jayandharan GR (2013) Bioengineering of AAV2 capsid at specific serine, threonine, or lysine residues improves its transduction efficiency in vitro and in vivo. Hum Gene Ther Methods 24(2):80–93. doi:10.1089/hgtb.2012.194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Sen D (2014) Improving clinical efficacy of adeno associated vectors by rational capsid bioengineering. J Biomed Sci 21:103. doi:10.1186/s12929-014-0103-1

    Article  PubMed  PubMed Central  Google Scholar 

  80. Hareendran S, Balakrishnan B, Sen D, Kumar S, Srivastava A, Jayandharan GR (2013) Adeno-associated virus (AAV) vectors in gene therapy: immune challenges and strategies to circumvent them. Rev Med Virol 23(6):399–413. doi:10.1002/rmv.1762

    Article  CAS  PubMed  Google Scholar 

  81. Mingozzi F, High KA (2013) Immune responses to AAV vectors: overcoming barriers to successful gene therapy. Blood 122(1):23–36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Li J, Wang D, Qian S, Chen Z, Zhu T, Xiao X (2003) Efficient and long-term intracardiac gene transfer in δ-sarcoglycan-deficiency hamster by adeno-associated virus-2 vectors. Gene Ther 10(21):1807–1813

    Article  CAS  PubMed  Google Scholar 

  83. Asfour B, Baba HA, Scheld HH, Hruban RH, Hammel D, Byrne BJ (2002) Uniform long-term gene expression using adeno-associated virus (AAV) by ex vivo recirculation in rat-cardiac isografts. Thorac Cardiovasc Surg 50(06):347–350

    Article  CAS  PubMed  Google Scholar 

  84. Kaspar BK, Roth DM, Chin Lai N, Drumm JD, Erickson DA, McKirnan MD, Hammond HK (2005) Myocardial gene transfer and long-term expression following intracoronary delivery of adeno-associated virus. The journal of gene medicine 7(3):316–324

    Article  CAS  PubMed  Google Scholar 

  85. Kaplitt MG, Xiao X, Samulski RJ, Li J, Ojamaa K, Klein IL, Makimura H, Kaplitt MJ, Strumpf RK, Diethrich EB (1996) Long-term gene transfer in porcine myocardium after coronary infusion of an adeno-associated virus vector. Ann Thorac Surg 62(6):1669–1676

    Article  CAS  PubMed  Google Scholar 

  86. Hoshijima M, Ikeda Y, Iwanaga Y, Minamisawa S, Date M-O, Gu Y, Iwatate M, Li M, Wang L, Wilson JM (2002) Chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV gene delivery. Nat Med 8(8):864–871

    CAS  PubMed  Google Scholar 

  87. Champion HC, Georgakopoulos D, Haldar S, Wang L, Wang Y, Kass DA (2003) Robust adenoviral and adeno-associated viral gene transfer to the in vivo murine heart application to study of phospholamban physiology. Circulation 108(22):2790–2797

    Article  CAS  PubMed  Google Scholar 

  88. Raake PW, Hinkel R, Müller S, Delker S, Kreuzpointner R, Kupatt C, Katus HA, Kleinschmidt JA, Boekstegers P, Müller OJ (2008) Cardio-specific long-term gene expression in a porcine model after selective pressure-regulated retroinfusion of adeno-associated viral (AAV) vectors. Gene Ther 15(1):12–17

    Article  CAS  PubMed  Google Scholar 

  89. Su LT, Gopal K, Wang Z, Yin X, Nelson A, Kozyak BW, Burkman JM, Mitchell MA, Low DW, Bridges CR (2005) Uniform scale-independent gene transfer to striated muscle after transvenular extravasation of vector. Circulation 112(12):1780–1788

    Article  CAS  PubMed  Google Scholar 

  90. Müller OJ, Schinkel S, Kleinschmidt A Jr, Katus HA, Bekeredjian R (2007) Ultrasound-targeted microbubble destruction augments adeno-associated virus (AAV)-mediated cardiac gene transfer after systemic administration in adult rats. Circulation 116(Suppl 16):II_65-II_65

    Google Scholar 

  91. Muller OJ, Schinkel S, Kleinschmidt JA, Katus HA, Bekeredjian R (2008) Augmentation of AAV-mediated cardiac gene transfer after systemic administration in adult rats. Gene Ther 15(23):1558–1565

    Article  CAS  PubMed  Google Scholar 

  92. Lipshutz GS, Gruber CA, Y-a C, Hardy J, Contag CH, Gaensler KML (2001) In utero delivery of adeno-associated viral vectors: intraperitoneal gene transfer produces long-term expression. Mol Ther 3(3):284

    Article  CAS  PubMed  Google Scholar 

  93. Katz MG, Fargnoli AS, Williams RD, Steuerwald NM, Isidro A, Ivanina AV, Sokolova IM, Bridges CR (2014) Safety and efficacy of high-dose adeno-associated virus 9 encoding sarcoplasmic reticulum Ca(2+) adenosine triphosphatase delivered by molecular cardiac surgery with recirculating delivery in ovine ischemic cardiomyopathy. J Thorac Cardiovasc Surg 148(3):1065–1072, 1073e1-2; discussion1072-3. doi:10.1016/jjtcvs201405070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Fargnoli AS, Katz MG, Williams RD, Margulies KB, Bridges CR (2014) A needleless liquid jet injection delivery method for cardiac gene therapy: a comparative evaluation versus standard routes of delivery reveals enhanced therapeutic retention and cardiac specific gene expression. J Cardiovasc Transl Res 7(8):756–767. doi:10.1007/s12265-014-9593-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Xiao W, Chirmule N, Schnell MA, Tazelaar J, Hughes JV, Wilson JM (2000) Route of administration determines induction of T-cell-independent humoral responses to adeno-associated virus vectors. Mol Ther 1(4):323

    Article  CAS  PubMed  Google Scholar 

  96. McCarty DM, Fu H, Monahan PE, Toulson CE, Naik P, Samulski RJ (2003) Adeno-associated virus terminal repeat (TR) mutant generates self-complementary vectors to overcome the rate-limiting step to transduction in vivo. Gene Ther 10(26):2112–2118

    Article  CAS  PubMed  Google Scholar 

  97. Wang Z, Ma H-I, Li J, Sun L, Zhang J, Xiao X (2003) Rapid and highly efficient transduction by double-stranded adeno-associated virus vectors in vitro and in vivo. Gene Ther 10(26):2105–2111

    Article  CAS  PubMed  Google Scholar 

  98. Prasad K-MR, Xu Y, Yang Z, Toufektsian M-C, Berr SS, French BA (2007) Topoisomerase inhibition accelerates gene expression after adeno-associated virus-mediated gene transfer to the mammalian heart. Mol Ther 15(4):764–771

    Article  CAS  Google Scholar 

  99. Wei X, Zhao C, Jiang J, Li J, Xiao X, Wang DW (2005) Adrenomedullin gene delivery alleviates hypertension and its secondary injuries of cardiovascular system. Hum Gene Ther 16(3):372–380

    Article  CAS  PubMed  Google Scholar 

  100. Aikawa R, Huggins GS, Snyder RO (2002) Cardiomyocyte-specific gene expression following recombinant adeno-associated viral vector transduction. J Biol Chem 277(21):18979–18985

    Article  CAS  PubMed  Google Scholar 

  101. Pacak CA, Sakai Y, Thattaliyath BD, Mah CS, Byrne BJ (2008) Tissue specific promoters improve specificity of AAV9 mediated transgene expression following intra-vascular gene delivery in neonatal mice. Genetic vaccines and therapy 6(1):1

    Article  CAS  Google Scholar 

  102. Phillips MI, Tang Y, Schmidt-Ott K, Qian K, Kagiyama S (2002) Vigilant vector: heart-specific promoter in an adeno-associated virus vector for cardioprotection. Hypertension 39(2):651–655

    Article  CAS  PubMed  Google Scholar 

  103. Pleger ST, Most P, Boucher M, Soltys S, Chuprun JK, Pleger W, Gao E, Dasgupta A, Rengo G, Remppis A (2007) Stable myocardial-specific AAV6-S100A1 gene therapy results in chronic functional heart failure rescue. Circulation 115(19):2506–2515

    Article  CAS  PubMed  Google Scholar 

  104. Su H, Arakawa-Hoyt J, Kan YW (2002) Adeno-associated viral vector-mediated hypoxia response element-regulated gene expression in mouse ischemic heart model. Proc Natl Acad Sci 99(14):9480–9485. doi:10.1073/pnas.132275299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Su H, Joho S, Huang Y, Barcena A, Arakawa-Hoyt J, Grossman W, Kan YW (2004) Adeno-associated viral vector delivers cardiac-specific and hypoxia-inducible VEGF expression in ischemic mouse hearts. Proc Natl Acad Sci U S A 101(46):16280–16285. doi:10.1073/pnas.0407449101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Ferrarini M, Arsic N, Recchia FA, Zentilin L, Zacchigna S, Xu X, Linke A, Giacca M, Hintze TH (2006) Adeno-associated virus-mediated transduction of VEGF165 improves cardiac tissue viability and functional recovery after permanent coronary occlusion in conscious dogs. Circ Res 98(7):954–961. doi:10.1161/01.res.0000217342.83731.89

    Article  CAS  PubMed  Google Scholar 

  107. Tao Z, Chen B, Tan X, Zhao Y, Wang L, Zhu T, Cao K, Yang Z, Kan YW, Su H (2011) Coexpression of VEGF and angiopoietin-1 promotes angiogenesis and cardiomyocyte proliferation reduces apoptosis in porcine myocardial infarction (MI) heart. Proc Natl Acad Sci U S A 108(5):2064–2069. doi:10.1073/pnas1018925108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Su H, Lu R, Kan YW (2000) Adeno-associated viral vector-mediated vascular endothelial growth factor gene transfer induces neovascular formation in ischemic heart. Proc Natl Acad Sci U S A 97(25):13801–13806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Beeri R, Chaput M, Guerrero JL, Kawase Y, Yosefy C, Abedat S, Karakikes I, Morel C, Tisosky A, Sullivan S (2010) Gene delivery of sarcoplasmic reticulum calcium ATPase inhibits ventricular remodeling in ischemic mitral regurgitation. Circulation: Heart Failure 3(5):627–634

    CAS  PubMed Central  Google Scholar 

  110. Kawase Y, Ly HQ, Prunier F, Lebeche D, Shi Y, Jin H, Hadri L, Yoneyama R, Hoshino K, Takewa Y, Sakata S, Peluso R, Zsebo K, Gwathmey JK, Tardif JC, Tanguay JF, Hajjar RJ (2008) Reversal of cardiac dysfunction after long-term expression of SERCA2a by gene transfer in a pre-clinical model of heart failure. J Am Coll Cardiol 51(11):1112–1119. doi:10.1016/jjacc200712014

    Article  CAS  PubMed  Google Scholar 

  111. Hadri L, Kratlian RG, Benard L, Maron BA, Dorfmuller P, Ladage D, Guignabert C, Ishikawa K, Aguero J, Ibanez B, Turnbull IC, Kohlbrenner E, Liang L, Zsebo K, Humbert M, Hulot JS, Kawase Y, Hajjar RJ, Leopold JA (2013) Therapeutic efficacy of AAV1.SERCA2a in monocrotaline-induced pulmonary arterial hypertension. Circulation 128(5):512–523. doi:10.1161/CIRCULATIONAHA113001585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Hadri L, Bobe R, Kawase Y, Ladage D, Ishikawa K, Atassi F, Lebeche D, Kranias EG, Leopold JA, Lompré A-M, Lipskaia L, Hajjar RJ (2009) SERCA2a gene transfer enhances eNOS expression and activity in endothelial cells. Mol Ther 18(7):1284–1292. doi:10.1038/mt.2010.77

    Article  CAS  Google Scholar 

  113. Pleger ST, Shan C, Ksienzyk J, Bekeredjian R, Boekstegers P, Hinkel R, Schinkel S, Leuchs B, Ludwig J, Qiu G, Weber C, Kleinschmidt A Jr, Raake P, Koch WJ, Katus HA, Müller OJ, Most P (2011) Cardiac AAV9-S100A1 gene therapy rescues postischemic heart failure in a preclinical large animal model. Sci Transl Med 3(92):92ra64–92ra64. doi:10.1126/scitranslmed.3002097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Tilemann L, Lee A, Ishikawa K, Aguero J, Rapti K, Santos-Gallego C, Kohlbrenner E, Fish KM, Kho C, Hajjar RJ (2013) SUMO-1 gene transfer improves cardiac function in a large-animal model of heart failure. Sci Transl Med 5(211):211ra159. doi:10.1126/scitranslmed3006487

    Article  PubMed  CAS  Google Scholar 

  115. Lee A, Jeong D, Mitsuyama S, Oh JG, Liang L, Ikeda Y, Sadoshima J, Hajjar RJ, Kho C (2014) The role of SUMO-1 in cardiac oxidative stress and hypertrophy. Antioxid Redox Signal 21(14):1986–2001. doi:10.1089/ars.2014.5983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Pachori AS, Melo LG, Zhang L, Solomon SD, Dzau VJ (2006) Chronic recurrent myocardial ischemic injury is significantly attenuated by pre-emptive adeno-associated virus heme oxygenase-1 gene delivery. J Am Coll Cardiol 47(3):635–643

    Article  CAS  PubMed  Google Scholar 

  117. Liu X, Pachori AS, Ward CA, Davis JP, Gnecchi M, Kong D, Zhang L, Murduck J, Yet SF, Perrella MA, Pratt RE, Dzau VJ, Melo LG (2006) Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores ventricular function. FASEB J 20(2):207–216

    Article  CAS  PubMed  Google Scholar 

  118. Liu X, Simpson JA, Brunt KR, Ward CA, Hall SR, Kinobe RT, Barrette V, Tse MY, Pang SC, Pachori AS, Dzau VJ, Ogunyankin KO, Melo LG (2007) Preemptive heme oxygenase-1 gene delivery reveals reduced mortality and preservation of left ventricular function 1 yr after acute myocardial infarction. Am J Physiol Heart Circ Physiol 293(1):H48–H59

    Article  CAS  PubMed  Google Scholar 

  119. Iwanaga Y, Hoshijima M, Gu Y, Iwatate M, Dieterle T, Ikeda Y, M-o D, Chrast J, Matsuzaki M, Peterson KL, Chien KR, Ross J (2004) Chronic phospholamban inhibition prevents progressive cardiac dysfunction and pathological remodeling after infarction in rats. J Clin Investig 113(5):727–736. doi:10.1172/jci200418716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Suckau L, Fechner H, Chemaly E, Krohn S, Hadri L, Kockskämper J, Westermann D, Bisping E, Ly H, Wang X, Kawase Y, Chen J, Liang L, Sipo I, Vetter R, Weger S, Kurreck J, Erdmann V, Tschope C, Pieske B, Lebeche D, Schultheiss H-P, Hajjar RJ, Poller WC (2009) Chronic cardiac-targeted RNA interference for the treatment of heart failure restores cardiac function and reduces pathological hypertrophy. Circulation 119(9):1241–1252. doi:10.1161/circulationaha.108.783852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Miyazaki Y, Ikeda Y, Shiraishi K, Fujimoto SN, Aoyama H, Yoshimura K, Inui M, Hoshijima M, Kasahara H, Aoki H, Matsuzaki M (2012) Heart failure-inducible gene therapy targeting protein phosphatase 1 prevents progressive left ventricular remodeling. PLoS One 7(4):e35875. doi:10.1371/journal.pone.0035875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Ishikawa K, Fish KM, Tilemann L, Rapti K, Aguero J, Santos-Gallego CG, Lee A, Karakikes I, Xie C, Akar FG, Shimada YJ, Gwathmey JK, Asokan A, McPhee S, Samulski J, Samulski RJ, Sigg DC, Weber T, Kranias EG, Hajjar RJ (2014) Cardiac I-1c overexpression with reengineered AAV improves cardiac function in swine ischemic heart failure. Mol Ther 22(12):2038–2045. doi:10.1038/mt2014127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Fish KM, Ladage D, Kawase Y, Karakikes I, Jeong D, Ly H, Ishikawa K, Hadri L, Tilemann L, Muller-Ehmsen J, Samulski RJ, Kranias EG, Hajjar RJ (2013) AAV9.I-1c delivered via direct coronary infusion in a porcine model of heart failure improves contractility and mitigates adverse remodelling. Circulation Heart failure 6(2):310–317. doi:10.1161/circheartfailure.112.971325

    Article  PubMed  Google Scholar 

  124. Jones SM, Hiller FC, Jacobi SE, Foreman SK, Pittman LM, Cornett LE (2003) Enhanced β(2)-adrenergic receptor (β(2)AR) signaling by adeno-associated viral (AAV)-mediated gene transfer. BMC Pharmacol 3:15–15. doi:10.1186/1471-2210-3-15

    Article  PubMed  PubMed Central  Google Scholar 

  125. Rengo G, Lymperopoulos A, Zincarelli C, Donniacuo M, Soltys S, Rabinowitz JE, Koch WJ (2009) Myocardial adeno-associated virus serotype 6-βARKct gene therapy improves cardiac function and normalizes the neurohormonal axis in chronic heart failure. Circulation 119(1):89–98. doi:10.1161/circulationaha.108.803999

    Article  CAS  PubMed  Google Scholar 

  126. Raake PWJ, Schlegel P, Ksienzyk J, Reinkober J, Barthelmes J, Schinkel S, Pleger S, Mier W, Haberkorn U, Koch WJ, Katus HA, Most P, Müller OJ (2013) AAV6.βARKct cardiac gene therapy ameliorates cardiac function and normalizes the catecholaminergic axis in a clinically relevant large animal heart failure model. Eur Heart J 34(19):1437–1447. doi:10.1093/eurheartj/ehr447

    Article  CAS  PubMed  Google Scholar 

  127. Huang BS, Chen A, Ahmad M, Wang H-W, Leenen FHH (2014) Mineralocorticoid and AT(1) receptors in the paraventricular nucleus contribute to sympathetic hyperactivity and cardiac dysfunction in rats post myocardial infarct. J Physiol 592(Pt 15):3273–3286. doi:10.1113/jphysiol.2014.276584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Karakikes I, Chaanine AH, Kang S, Mukete BN, Jeong D, Zhang S, Hajjar RJ, Lebeche D (2013) Therapeutic cardiac-targeted delivery of miR-1 reverses pressure overload-induced cardiac hypertrophy and attenuates pathological remodeling. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease 2(2):e000078. doi:10.1161/jaha.113.000078

    Article  Google Scholar 

  129. Wahlquist C, Jeong D, Rojas-Muñoz A, Kho C, Lee A, Mitsuyama S, van Mil A, Jin Park W, Sluijter JPG, Doevendans PAF, Hajjar RJ, Mercola M (2014) Inhibition of miR-25 improves cardiac contractility in the failing heart. Nature 508(7497):531–535. doi:10.1038/nature13073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Ganesan J, Ramanujam D, Sassi Y, Ahles A, Jentzsch C, Werfel S, Leierseder S, Loyer X, Giacca M, Zentilin L, Thum T, Laggerbauer B, Engelhardt S (2013) MiR-378 controls cardiac hypertrophy by combined repression of mitogen-activated protein kinase pathway factors. Circulation 127(21):2097–2106. doi:10.1161/CIRCULATIONAHA112000882

    Article  CAS  PubMed  Google Scholar 

  131. Denegri M, Bongianino R, Lodola F, Boncompagni S, De Giusti VC, Avelino-Cruz JE, Liu N, Persampieri S, Curcio A, Esposito F, Pietrangelo L, Marty I, Villani L, Moyaho A, Baiardi P, Auricchio A, Protasi F, Napolitano C, Priori SG (2014) Single delivery of an adeno-associated viral construct to transfer the CASQ2 gene to knock-in mice affected by catecholaminergic polymorphic ventricular tachycardia is able to cure the disease from birth to advanced age. Circulation 129(25):2673–2681. doi:10.1161/CIRCULATIONAHA113006901

    Article  CAS  PubMed  Google Scholar 

  132. Kawada T, Sakamoto A, Nakazawa M, Urabe M, Masuda F, Hemmi C, Wang Y, Soo Shin W, Nakatsuru Y, Sato H, Ozawa K, Toyo-oka T (2001) Morphological and physiological restorations of hereditary form of dilated cardiomyopathy by somatic gene therapy. Biochem Biophys Res Commun 284(2):431–435. doi:10.1006/bbrc.2001.4962

    Article  CAS  PubMed  Google Scholar 

  133. Zhu T, Zhou L, Mori S, Wang Z, McTiernan CF, Qiao C, Chen C, Wang DW, Li J, Xiao X (2005) Sustained whole-body functional rescue in congestive heart failure and muscular dystrophy hamsters by systemic gene transfer. Circulation 112(17):2650–2659

    Article  CAS  PubMed  Google Scholar 

  134. Dandapat A, Hu CP, Li D, Liu Y, Chen H, Hermonat PL, Mehta JL (2008) Overexpression of TGFbeta1 by adeno-associated virus type-2 vector protects myocardium from ischemia-reperfusion injury. Gene Ther 15(6):415–423

    Article  CAS  PubMed  Google Scholar 

  135. Squadrito F, Deodato B, Squadrito G, Seminara P, Passaniti M, Venuti FS, Giacca M, Minutoli L, Adamo EB, Bellomo M, Marini R, Galeano M, Marini H, Altavilla D (2003) Gene transfer of IkappaBalpha limits infarct size in a mouse model of myocardial ischemia-reperfusion injury. Lab Investig 83(8):1097–1104

    Article  CAS  PubMed  Google Scholar 

  136. Agrawal RS, Muangman S, Layne MD, Melo L, Perrella MA, Lee RT, Zhang L, Lopez-Ilasaca M, Dzau VJ (2004) Pre-emptive gene therapy using recombinant adeno-associated virus delivery of extracellular superoxide dismutase protects heart against ischemic reperfusion injury, improves ventricular function and prolongs survival. Gene Ther 11(12):962–969

    Article  CAS  PubMed  Google Scholar 

  137. Belke DD, Gloss B, Hollander JM, Swanson EA, Duplain H, Dillmann WH (2006) In vivo gene delivery of HSP70i by adenovirus and adeno-associated virus preserves contractile function in mouse heart following ischemia-reperfusion. Am J Physiol Heart Circ Physiol 291(6):H2905–H2910

    Article  CAS  PubMed  Google Scholar 

  138. Zhao XY, Hu SJ, Li J, Mou Y, Chan CF, Jin J, Sun J, Zhu ZH (2006) rAAV-mediated angiogenin gene transfer induces angiogenesis and modifies left ventricular remodeling in rats with myocardial infarction. J Mol Med (Berl) 84(12):1033–1046

    Article  CAS  Google Scholar 

  139. Kusano K, Tsutsumi Y, Dean J, Gavin M, Ma H, Silver M, Thorne T, Zhu Y, Losordo DW, Aikawa R (2007) Long-term stable expression of human growth hormone by rAAV promotes myocardial protection post-myocardial infarction. J Mol Cell Cardiol 42(2):390–399

    Article  CAS  PubMed  Google Scholar 

  140. Yasukawa H, Yajima T, Duplain H, Iwatate M, Kido M, Hoshijima M, Weitzman MD, Nakamura T, Woodard S, Xiong D, Yoshimura A, Chien KR, Knowlton KU (2003) The suppressor of cytokine signaling-1 (SOCS1) is a novel therapeutic target for enterovirus-induced cardiac injury. J Clin Invest 111(4):469–478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Tsui TY, Wu X, Lau CK, Ho DW, Xu T, Siu YT, Fan ST (2003) Prevention of chronic deterioration of heart allograft by recombinant adeno-associated virus-mediated heme oxygenase-1 gene transfer. Circulation 107(20):2623–2629

    CAS  PubMed  Google Scholar 

  142. Chen Z, Lu L, Li J, Xiao X, Fung JJ, Qian S (2003) Prolonged survival of heart allografts transduced with AAV-CTLA4Ig. Microsurgery 23(5):489–493

    Article  PubMed  Google Scholar 

  143. Kodirov SA, Brunner M, Busconi L, Koren G (2003) Long-term restitution of 4-aminopyridine-sensitive currents in Kv1DN ventricular myocytes using adeno-associated virus-mediated delivery of Kv1.5. FEBS Lett 550(1–3):74–78

    Article  CAS  PubMed  Google Scholar 

  144. Bostick B, Yue Y, Lai Y, Long C, Li D, Duan D (2008) Adeno-associated virus serotype-9 microdystrophin gene therapy ameliorates electrocardiographic abnormalities in mdx mice. Hum Gene Ther 19(8):851–856. doi:10.1089/hum2008058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Yue Y, Li Z, Harper SQ, Davisson RL, Chamberlain JS, Duan D (2003) Microdystrophin gene therapy of cardiomyopathy restores dystrophin-glycoprotein complex and improves sarcolemma integrity in the mdx mouse heart. Circulation 108(13):1626–1632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Hikoso S, Ikeda Y, Yamaguchi O, Takeda T, Higuchi Y, Hirotani S, Kashiwase K, Yamada M, Asahi M, Matsumura Y, Nishida K, Matsuzaki M, Hori M, Otsu K (2007) Progression of heart failure was suppressed by inhibition of apoptosis signal-regulating kinase 1 via transcoronary gene transfer. J Am Coll Cardiol 50(5):453–462

    Article  CAS  PubMed  Google Scholar 

  147. Nykanen AI, Pajusola K, Krebs R, Keranen MA, Raisky O, Koskinen PK, Alitalo K, Lemstrom KB (2006) Common protective and diverse smooth muscle cell effects of AAV-mediated angiopoietin-1 and -2 expression in rat cardiac allograft vasculopathy. Circ Res 98(11):1373–1380

    Article  PubMed  CAS  Google Scholar 

  148. Merritt JL II, Nguyen T, Daniels J, Matern D, Schowalter DB (2009) Biochemical correction of very long-chain acyl-CoA dehydrogenase deficiency following adeno-associated virus gene therapy. Mol Ther 17(3):425–429. doi:10.1038/mt2008295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Sferra TJ, Backstrom K, Wang C, Rennard R, Miller M, Hu Y (2004) Widespread correction of lysosomal storage following intrahepatic injection of a recombinant adeno-associated virus in the adult MPS VII mouse. Mol Ther 10(3):478–491

    Article  CAS  PubMed  Google Scholar 

  150. Takahashi H, Hirai Y, Migita M, Seino Y, Fukuda Y, Sakuraba H, Kase R, Kobayashi T, Hashimoto Y, Shimada T (2002) Long-term systemic therapy of Fabry disease in a knockout mouse by adeno-associated virus-mediated muscle-directed gene transfer. Proc Natl Acad Sci U S A 99(21):13777–13782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Jung SC, Han IP, Limaye A, Xu R, Gelderman MP, Zerfas P, Tirumalai K, Murray GJ, During MJ, Brady RO, Qasba P (2001) Adeno-associated viral vector-mediated gene transfer results in long-term enzymatic and functional correction in multiple organs of Fabry mice. Proc Natl Acad Sci U S A 98(5):2676–2681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Park J, Murray GJ, Limaye A, Quirk JM, Gelderman MP, Brady RO, Qasba P (2003) Long-term correction of globotriaosylceramide storage in Fabry mice by recombinant adeno-associated virus-mediated gene transfer. Proc Natl Acad Sci U S A 100(6):3450–3454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Collesi C, Zentilin L, Sinagra G, Giacca M (2008) Notch1 signaling stimulates proliferation of immature cardiomyocytes. J Cell Biol 183(1):117–128. doi:10.1083/jcb200806091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Bao C, Guo J, Lin G, Hu M, Hu Z (2008) TNFR gene-modified mesenchymal stem cells attenuate inflammation and cardiac dysfunction following MI. Scand Cardiovasc J 42(1):56–62

    Article  CAS  PubMed  Google Scholar 

  155. Packer M (1988) Neurohormonal interactions and adaptations in congestive heart failure. Circulation 77(4):721–730. doi:10.1161/01.cir.77.4.721

    Article  CAS  PubMed  Google Scholar 

  156. Esposito G, Rapacciuolo A, Naga Prasad SV, Takaoka H, Thomas SA, Koch WJ, Rockman HA (2002) Genetic alterations that inhibit in vivo pressure-overload hypertrophy prevent cardiac dysfunction despite increased wall stress. Circulation 105(1):85–92. doi:10.1161/hc0102.101365

    Article  CAS  PubMed  Google Scholar 

  157. Grossman W, Jones D, McLaurin LP (1975) Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Investig 56(1):56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Chien KR (2000) Genomic circuits and the integrative biology of cardiac diseases. Nature 407(6801):227–232

    Article  CAS  PubMed  Google Scholar 

  159. Katz AM (1997) Evolving concepts of heart failure: cooling furnace, malfunctioning pump, enlarging muscle—part I. J Card Fail 3(4):319–334

    Article  CAS  PubMed  Google Scholar 

  160. Esler M, Kaye D, Lambert G, Esler D, Jennings G (1997) Adrenergic nervous system in heart failure. Am J Cardiol 80(11):7L–14L

    Article  CAS  PubMed  Google Scholar 

  161. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP (1990) Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 322(22):1561–1566

    Article  CAS  PubMed  Google Scholar 

  162. Engelhardt S, Hein L, Wiesmann F, Lohse MJ (1999) Progressive hypertrophy and heart failure in β1-adrenergic receptor transgenic mice. Proc Natl Acad Sci 96(12):7059–7064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Engelhardt S, Hein L, Dyachenkow V, Kranias EG, Isenberg G, Lohse MJ (2004) Altered calcium handling is critically involved in the cardiotoxic effects of chronic β-adrenergic stimulation. Circulation 109(9):1154–1160

    Article  CAS  PubMed  Google Scholar 

  164. Milano CA, Allen LF, Rockman HA, Dolber PC, McMinn TR, Chien KR, Johnson TD, Bond RA, Lefkowitz RJ (1994) Enhanced myocardial function in transgenic mice overexpressing the beta 2-adrenergic receptor. Science 264(5158):582–586. doi:10.1126/science.8160017

    Article  CAS  PubMed  Google Scholar 

  165. Akhter SA, Skaer CA, Kypson AP, McDonald PH, Peppel KC, Glower DD, Lefkowitz RJ, Koch WJ (1997) Restoration of β-adrenergic signaling in failing cardiac ventricular myocytes via adenoviral-mediated gene transfer. Proc Natl Acad Sci 94(22):12100–12105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Dorn GW, Tepe NM, Lorenz JN, Koch WJ, Liggett SB (1999) Low-and high-level transgenic expression of β2-adrenergic receptors differentially affect cardiac hypertrophy and function in Gαq-overexpressing mice. Proc Natl Acad Sci 96(11):6400–6405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Freeman K, Lerman I, Kranias EG, Bohlmeyer T, Bristow MR, Lefkowitz RJ, Iaccarino G, Koch WJ, Leinwand LA (2001) Alterations in cardiac adrenergic signaling and calcium cycling differentially affect the progression of cardiomyopathy. J Clin Invest 107(8):967–974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Du X-J, Autelitano DJ, Dilley RJ, Wang B, Dart AM, Woodcock EA (2000) β2-adrenergic receptor overexpression exacerbates development of heart failure after aortic stenosis. Circulation 101(1):71–77

    Article  CAS  PubMed  Google Scholar 

  169. Koch WJ, Rockman HA, Samama P, Hamilton R (1995) Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a BetaARK inhibitor. Science 268(5215):1350

    Article  CAS  PubMed  Google Scholar 

  170. Shah AS, White DC, Emani S, Kypson AP, Lilly RE, Wilson K, Glower DD, Lefkowitz RJ, Koch WJ (2001) In vivo ventricular gene delivery of a β-adrenergic receptor kinase inhibitor to the failing heart reverses cardiac dysfunction. Circulation 103(9):1311–1316

    Article  CAS  PubMed  Google Scholar 

  171. Bristow MR (1998) Why does the myocardium fail? Insights from basic science. Lancet 352:SI8–SI14

    Article  PubMed  Google Scholar 

  172. Emani SM, Shah AS, White DC, Glower DD, Koch WJ (2001) Right ventricular gene therapy with a β-adrenergic receptor kinase inhibitor improves survival after pulmonary artery banding. Ann Thorac Surg 72(5):1657–1661

    Article  CAS  PubMed  Google Scholar 

  173. Tevaearai HT, Eckhart AD, Shotwell KF, Wilson K, Koch WJ (2001) Ventricular dysfunction after cardioplegic arrest is improved after myocardial gene transfer of a β-adrenergic receptor kinase inhibitor. Circulation 104(17):2069–2074. doi:10.1161/hc4201.097188

    Article  CAS  PubMed  Google Scholar 

  174. Rengo G, Perrone-Filardi P, Femminella GD, Liccardo D, Zincarelli C, de Lucia C, Pagano G, Marsico F, Lymperopoulos A, Leosco D (2000) Targeting the β-adrenergic receptor system through G-protein-coupled receptor kinase 2: a new paradigm for therapy and prognostic evaluation in heart failure. From Bench to Bedside 5(3):385–391. doi:10.1161/circheartfailure.112.966895

    Google Scholar 

  175. Williams ML, Hata JA, Schroder J, Rampersaud E, Petrofski J, Jakoi A, Milano CA, Koch WJ (2004) Targeted β-adrenergic receptor kinase (βARK1) inhibition by gene transfer in failing human hearts. Circulation 109(13):1590–1593

    Article  CAS  PubMed  Google Scholar 

  176. Gao MH, Lai NC, Roth DM, Zhou J, Zhu J, Anzai T, Dalton N, Hammond HK (1999) Adenylylcyclase increases responsiveness to catecholamine stimulation in transgenic mice. Circulation 99(12):1618–1622

    Article  CAS  PubMed  Google Scholar 

  177. Lai NC, Roth DM, Gao MH, Tang T, Dalton N, Lai YY, Spellman M, Clopton P, Hammond HK (2004) Intracoronary adenovirus encoding adenylyl cyclase VI increases left ventricular function in heart failure. Circulation 110(3):330–336

    Article  CAS  PubMed  Google Scholar 

  178. Lai NC, Roth DM, Gao MH, Fine S, Head BP, Zhu J, McKirnan MD, Kwong C, Dalton N, Urasawa K, Roth DA, Hammond HK (2000) Intracoronary delivery of adenovirus encoding adenylyl cyclase VI increases left ventricular function and cAMP-generating capacity. Circulation 102(19):2396–2401

    Article  CAS  PubMed  Google Scholar 

  179. Crackower MA, Oudit GY, Kozieradzki I, Sarao R, Sun H, Sasaki T, Hirsch E, Suzuki A, Shioi T, Irie-Sasaki J, Sah R, Cheng HY, Rybin VO, Lembo G, Fratta L, Oliveira-dos-Santos AJ, Benovic JL, Kahn CR, Izumo S, Steinberg SF, Wymann MP, Backx PH, Penninger JM (2002) Regulation of myocardial contractility and cell size by distinct PI3K-PTEN signaling pathways. Cell 110(6):737–749

    Article  CAS  PubMed  Google Scholar 

  180. Rameh LE, Cantley LC (1999) The role of phosphoinositide 3-kinase lipid products in cell function. J Biol Chem 274(13):8347–8350

    Article  CAS  PubMed  Google Scholar 

  181. Shioi T, Kang PM, Douglas PS, Hampe J, Yballe CM, Lawitts J, Cantley LC, Izumo S (2000) The conserved phosphoinositide 3-kinase pathway determines heart size in mice. EMBO J 19(11):2537–2548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Naga Prasad SV, Laporte SA, Chamberlain D, Caron MG, Barak L, Rockman HA (2002) Phosphoinositide 3-kinase regulates beta2-adrenergic receptor endocytosis by AP-2 recruitment to the receptor/beta-arrestin complex. J Cell Biol 158(3):563–575

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  183. Perrino C, Naga Prasad SV, Patel M, Wolf MJ, Rockman HA (2005) Targeted inhibition of beta-adrenergic receptor kinase-1-associated phosphoinositide-3 kinase activity preserves beta-adrenergic receptor signaling and prolongs survival in heart failure induced by calsequestrin overexpression. J Am Coll Cardiol 45(11):1862–1870

    Article  CAS  PubMed  Google Scholar 

  184. Schmidt U, Hajjar RJ, Kim CS, Lebeche D, Doye AA, Gwathmey JK (1999) Human heart failure: cAMP stimulation of SR Ca(2+)-ATPase activity and phosphorylation level of phospholamban. Am J Phys 277(2 Pt 2):H474–H480

    CAS  Google Scholar 

  185. Lompre AM, Lambert F, Lakatta EG, Schwartz K (1991) Expression of sarcoplasmic reticulum Ca(2+)-ATPase and calsequestrin genes in rat heart during ontogenic development and aging. Circ Res 69(5):1380–1388

    Article  CAS  PubMed  Google Scholar 

  186. Hasenfuss G, Reinecke H, Studer R, Meyer M, Pieske B, Holtz J, Holubarsch C, Posival H, Just H, Drexler H (1994) Relation between myocardial function and expression of sarcoplasmic reticulum Ca(2+)-ATPase in failing and nonfailing human myocardium. Circ Res 75(3):434–442

    Article  CAS  PubMed  Google Scholar 

  187. van Berlo JH, Maillet M, Molkentin JD (2013) Signaling effectors underlying pathologic growth and remodeling of the heart. J Clin Invest 123(1):37–45. doi:10.1172/JCI62839

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  188. Distefano G, Sciacca P (2012) Molecular pathogenesis of myocardial remodeling and new potential therapeutic targets in chronic heart failure. Ital J Pediatr 38:41. doi:10.1186/1824-7288-38-41

    Article  PubMed  PubMed Central  Google Scholar 

  189. Gwathmey JK, Copelas L, MacKinnon R, Schoen FJ, Feldman MD, Grossman W, Morgan JP (1987) Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure. Circ Res 61(1):70–76

    Article  CAS  PubMed  Google Scholar 

  190. Zarain-Herzberg A (2006) Regulation of the sarcoplasmic reticulum Ca2+-ATPase expression in the hypertrophic and failing heart. Can J Physiol Pharmacol 84(5):509–521

    Article  CAS  PubMed  Google Scholar 

  191. Zarain-Herzberg A, Estrada-Aviles R, Fragoso-Medina J (2012) Regulation of sarco(endo)plasmic reticulum Ca2+-ATPase and calsequestrin gene expression in the heart. Can J Physiol Pharmacol 90(8):1017–1028. doi:10.1139/y2012-057

    Article  CAS  PubMed  Google Scholar 

  192. Frank KF, Bolck B, Erdmann E, Schwinger RH (2003) Sarcoplasmic reticulum Ca2+-ATPase modulates cardiac contraction and relaxation. Cardiovasc Res 57(1):20–27

    Article  CAS  PubMed  Google Scholar 

  193. Winslow RL, Rice J, Jafri S, Marban E, O'Rourke B (1999) Mechanisms of altered excitation-contraction coupling in canine tachycardia-induced heart failure, II: model studies. Circ Res 84(5):571–586

    Article  CAS  PubMed  Google Scholar 

  194. Lompre AM, Hajjar RJ, Harding SE, Kranias EG, Lohse MJ, Marks AR (2010) Ca2+ cycling and new therapeutic approaches for heart failure. Circulation 121(6):822–830. doi:10.1161/CIRCULATIONAHA109890954

    Article  PubMed  PubMed Central  Google Scholar 

  195. del Monte F, Williams E, Lebeche D, Schmidt U, Rosenzweig A, Gwathmey JK, Lewandowski ED, Hajjar RJ (2001) Improvement in survival and cardiac metabolism after gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase in a rat model of heart failure. Circulation 104(12):1424–1429

    Article  PubMed  PubMed Central  Google Scholar 

  196. Prunier F, Kawase Y, Gianni D, Scapin C, Danik SB, Ellinor PT, Hajjar RJ, Del Monte F (2008) Prevention of ventricular arrhythmias with sarcoplasmic reticulum Ca2+ ATPase pump overexpression in a porcine model of ischemia reperfusion. Circulation 118(6):614–624. doi:10.1161/CIRCULATIONAHA108770883

    Article  CAS  PubMed  Google Scholar 

  197. Sakata S, Lebeche D, Sakata N, Sakata Y, Chemaly ER, Liang LF, Tsuji T, Takewa Y, del Monte F, Peluso R, Zsebo K, Jeong D, Park WJ, Kawase Y, Hajjar RJ (2007) Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins. J Mol Cell Cardiol 42(4):852–861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Miyamoto MI, del Monte F, Schmidt U, DiSalvo TS, Kang ZB, Matsui T, Guerrero JL, Gwathmey JK, Rosenzweig A, Hajjar RJ (2000) Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure. Proc Natl Acad Sci U S A 97(2):793–798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Federica del M, Harding SE, Schmidt U, Matsui T, Kang ZB, Dec GW, Gwathmey JK, Rosenzweig A, Hajjar RJ (1999) Restoration of contractile function in isolated cardiomyocytes from failing human hearts by gene transfer of SERCA2a. Circulation 100(23):2308–2311. doi:10.1161/01.cir.100.23.2308

    Article  Google Scholar 

  200. Hui HP, Li XY, Liu XH, Sun S, Lu XC, Liu T, Yang W (2006) Adeno-associated viral gene transfer of SERCA2a improves heart function in chronic congestive heart failure rats. Zhonghua Xin Xue Guan Bing Za Zhi 34(4):357–362

    CAS  PubMed  Google Scholar 

  201. Haghighi K, Bidwell P, Kranias EG (2014) Phospholamban interactome in cardiac contractility and survival: a new vision of an old friend. J Mol Cell Cardiol 77:160–167. doi:10.1016/jyjmcc201410005

    Article  CAS  PubMed  Google Scholar 

  202. Kranias EG, Hajjar RJ (2012) Modulation of cardiac contractility by the phopholamban/SERCA2a regulatome. Circ Res 110(12):1646–1660. doi:10.1161/circresaha.111.259754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Carr AN, Schmidt AG, Suzuki Y, del Monte F, Sato Y, Lanner C, Breeden K, Jing S-L, Allen PB, Greengard P, Yatani A, Hoit BD, Grupp IL, Hajjar RJ, DePaoli-Roach AA, Kranias EG (2002) Type 1 phosphatase, a negative regulator of cardiac function. Mol Cell Biol 22(12):4124–4135. doi:10.1128/mcb.22.12.4124-4135.2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Chiang DY, Heck AJR, Dobrev D, Wehrens XHT (2016) Regulating the regulator: insights into the cardiac protein phosphatase 1 interactome. J Mol Cell Cardiol 101:165–172

    Article  CAS  PubMed  Google Scholar 

  205. Pathak A, del Monte F, Zhao W, Schultz J-E, Lorenz JN, Bodi I, Weiser D, Hahn H, Carr AN, Syed F, Mavila N, Jha L, Qian J, Marreez Y, Chen G, McGraw DW, Heist EK, Guerrero JL, DePaoli-Roach AA, Hajjar RJ, Kranias EG (2005) Enhancement of cardiac function and suppression of heart failure progression by inhibition of protein phosphatase 1. Circ Res 96(7):756–766. doi:10.1161/01.RES.0000161256.85833.fa

    Article  CAS  PubMed  Google Scholar 

  206. Nicolaou P, Rodriguez P, Ren X, Zhou X, Qian J, Sadayappan S, Mitton B, Pathak A, Robbins J, Hajjar RJ, Jones K, Kranias EG (2009) Inducible expression of active protein phosphatase-1 inhibitor-1 enhances basal cardiac function and protects against ischemia/reperfusion injury. Circ Res 104(8):1012–1020. doi:10.1161/circresaha.108.189811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Lipskaia L, Bobe R, Chen J, Turnbull IC, Lopez JJ, Merlet E, Jeong D, Karakikes I, Ross AS, Liang L, Mougenot N, Atassi F, Lompre AM, Tarzami ST, Kovacic JC, Kranias E, Hajjar RJ, Hadri L (2014) Synergistic role of protein phosphatase inhibitor 1 and sarco/endoplasmic reticulum Ca2+-ATPase in the acquisition of the contractile phenotype of arterial smooth muscle cells. Circulation 129(7):773–785. doi:10.1161/CIRCULATIONAHA113002565

    Article  CAS  PubMed  Google Scholar 

  208. Kraus C, Rohde D, Weidenhammer C, Qiu G, Pleger ST, Voelkers M, Boerries M, Remppis A, Katus HA, Most P (2009) S100A1 in cardiovascular health and disease: “closing the gap between basic science and clinical therapy”. J Mol Cell Cardiol 47(4):445–455. doi:10.1016/j.yjmcc.2009.06.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Most P, Seifert H, Gao E, Funakoshi H, Völkers M, Heierhorst JR, Remppis A, Pleger ST, DeGeorge BR, Eckhart AD, Feldman AM, Koch WJ (2006) Cardiac S100A1 protein levels determine contractile performance and propensity toward heart failure after myocardial infarction. Circulation 114(12):1258–1268. doi:10.1161/circulationaha.106.622415

    Article  CAS  PubMed  Google Scholar 

  210. Kho C, Lee A, Jeong D, Oh JG, Chaanine AH, Kizana E, Park WJ, Hajjar RJ (2011) SUMO1-dependent modulation of SERCA2a in heart failure. Nature 477(7366):601–605. doi:10.1038/nature10407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  211. Kho C, Lee A, Jeong D, Oh JG, Gorski PA, Fish K, Sanchez R, DeVita RJ, Christensen G, Dahl R, Hajjar RJ (2015) Small-molecule activation of SERCA2a SUMOylation for the treatment of heart failure. Nat Commun 6:7229. doi:10.1038/ncomms8229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Maeda Y, Ikeda U, Shimpo M, Shibuya M, Monahan J, Urabe M, Ozawa K, Shimada K (2000) Adeno-associated virus-mediated vascular endothelial growth factor gene transfer into cardiac myocytes. J Cardiovasc Pharmacol 36(4):438–443

    Article  CAS  PubMed  Google Scholar 

  213. Kawada T, Nakazawa M, Nakauchi S, Yamazaki K, Shimamoto R, Urabe M, Nakata J, Hemmi C, Masui F, Nakajima T, Suzuki J, Monahan J, Sato H, Masaki T, Ozawa K, Toyo-Oka T (2002) Rescue of hereditary form of dilated cardiomyopathy by rAAV-mediated somatic gene therapy: amelioration of morphological findings, sarcolemmal permeability, cardiac performances, and the prognosis of TO-2 hamsters. Proc Natl Acad Sci U S A 99(2):901–906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. van Rooij E (2011) The art of microRNA research. Circ Res 108(2):219–234. doi:10.1161/CIRCRESAHA110227496

    Article  PubMed  CAS  Google Scholar 

  215. Divakaran V, Mann DL (2008) The emerging role of MicroRNAs in cardiac remodeling and heart failure. Circ Res 103(10):1072–1083. doi:10.1161/circresaha.108.183087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Piras BA, O’Connor DM, French BA (2013) Systemic delivery of shRNA by AAV9 provides highly efficient knockdown of ubiquitously expressed GFP in mouse heart, but not liver. PLoS One 8(9):e75894. doi:10.1371/journal.pone.0075894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  217. Li M, Jayandharan GR, Li B, Ling C, Ma W, Srivastava A, Zhong L (2010) High-efficiency transduction of fibroblasts and mesenchymal stem cells by tyrosine-mutant AAV2 vectors for their potential use in cellular therapy. Hum Gene Ther 21(11):1527–1543. doi:10.1089/hum2010005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  218. Kauss MA, Smith LJ, Zhong L, Srivastava A, Wong KK Jr, Chatterjee S (2010) Enhanced long-term transduction and multilineage engraftment of human hematopoietic stem cells transduced with tyrosine-modified recombinant adeno-associated virus serotype 2. Hum Gene Ther 21(9):1129–1136. doi:10.1089/hum2010016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  219. Hacein-Bey-Abina S, Hauer J, Lim A, Picard C, Wang GP, Berry CC, Martinache C, Rieux-Laucat F, Latour S, Belohradsky BH, Leiva L, Sorensen R, Debre M, Casanova JL, Blanche S, Durandy A, Bushman FD, Fischer A, Cavazzana-Calvo M (2010) Efficacy of gene therapy for X-linked severe combined immunodeficiency. N Engl J Med 363(4):355–364. doi:10.1056/NEJMoa1000164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  220. Cavazzana-Calvo M, Hacein-Bey S, de Saint BG, Gross F, Yvon E, Nusbaum P, Selz F, Hue C, Certain S, Casanova JL, Bousso P, Deist FL, Fischer A (2000) Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 288(5466):669–672

    Article  CAS  PubMed  Google Scholar 

  221. Neven B, Leroy S, Decaluwe H, Le Deist F, Picard C, Moshous D, Mahlaoui N, Debre M, Casanova JL, Dal Cortivo L, Madec Y, Hacein-Bey-Abina S, de Saint BG, de Villartay JP, Blanche S, Cavazzana-Calvo M, Fischer A (2009) Long-term outcome after hematopoietic stem cell transplantation of a single-center cohort of 90 patients with severe combined immunodeficiency. Blood 113(17):4114–4124. doi:10.1182/blood-2008-09-177923

    Article  CAS  PubMed  Google Scholar 

  222. Wilson JM (2009) Lessons learned from the gene therapy trial for ornithine transcarbamylase deficiency. Mol Genet Metab 96(4):151–157. doi:10.1016/jymgme200812016

    Article  CAS  PubMed  Google Scholar 

  223. Hajjar RJ, Zsebo K, Deckelbaum L, Thompson C, Rudy J, Yaroshinsky A, Ly H, Kawase Y, Wagner K, Borow K, Jaski B, London B, Greenberg B, Pauly DF, Patten R, Starling R, Mancini D, Jessup M (2008) Design of a phase 1/2 trial of intracoronary administration of AAV1/SERCA2a in patients with heart failure. J Card Fail 14(5):355–367. doi:10.1016/jcardfail200802005

    Article  CAS  PubMed  Google Scholar 

  224. Jessup M, Greenberg B, Mancini D, Cappola T, Pauly DF, Jaski B, Yaroshinsky A, Zsebo KM, Dittrich H, Hajjar RJ (2011) Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure. Circulation 124(3):304–313. doi:10.1161/CIRCULATIONAHA111022889

    Article  CAS  PubMed  Google Scholar 

  225. Greenberg B, Yaroshinsky A, Zsebo KM, Butler J, Felker GM, Voors AA, Rudy JJ, Wagner K, Hajjar RJ (2014) Design of a phase 2b trial of intracoronary administration of AAV1/SERCA2a in patients with advanced heart failure: the CUPID 2 trial (calcium up-regulation by percutaneous administration of gene therapy in cardiac disease phase 2b). JACC Heart Fail 2(1):84–92. doi:10.1016/jjchf201309008

    Article  PubMed  Google Scholar 

  226. Greenberg B, Butler J, Felker GM, Ponikowski P, Voors AA, Desai AS, Barnard D, Bouchard A, Jaski B, Lyon AR, Pogoda JM, Rudy JJ, Zsebo KM (2016) Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial. Lancet 387(10024):1178–1186. doi:10.1016/s0140-6736(16)00082-9

    Article  CAS  PubMed  Google Scholar 

  227. Greenberg B, Butler J, Felker GM, Ponikowski P, Voors AA, Jaski B, Lyon AR, Pogoda JM, Rudy JJ, Zsebo KM (2015) CUPID 2: a phase 2b trial investigating the efficacy and safety of the intracoronary administration of AAV1/SERCA2a in patients with advanced heart failure. J Card Fail 21(11):939–940. doi:10.1016/j.cardfail.2015.09.012

    Article  Google Scholar 

  228. Hulot JS, Salem JE, Redheuil A, Collet JP, Varnous S, Jourdain P, Logeart D, Gandjbakhch E, Bernard C, Hatem SN, Isnard R, Cluzel P, Le Feuvre C, Leprince P, Hammoudi N, Lemoine FM, Klatzmann D, Vicaut E, Komajda M, Montalescot G, Lompre AM, Hajjar RJ (2017) Effect of intracoronary administration of AAV1/SERCA2a on ventricular remodelling in patients with advanced systolic heart failure: results from the AGENT-HF randomized phase 2 trial. Eur J Heart Fail. doi:10.1002/ejhf826

  229. Zsebo K, Yaroshinsky A, Rudy JJ, Wagner K, Greenberg B, Jessup M, Hajjar RJ (2014) Long-term effects of AAV1/SERCA2a gene transfer in patients with severe heart failure: analysis of recurrent cardiovascular events and mortality. Circ Res 114(1):101–108. doi:10.1161/CIRCRESAHA113302421

    Article  CAS  PubMed  Google Scholar 

  230. Chatterjee S, Stewart AS, Bish LT, Jayasankar V, Kim EM, Pirolli T, Burdick J, Woo YJ, Gardner TJ, Sweeney HL (2002) Viral gene transfer of the antiapoptotic factor Bcl-2 protects against chronic postischemic heart failure. Circulation 106(12 suppl 1):I-212–I-217. doi:10.1161/01.cir.0000032907.33237.55

    Google Scholar 

  231. Li W, Ma N, Ong LL, Nesselmann C, Klopsch C, Ladilov Y, Furlani D, Piechaczek C, Moebius JM, Lützow K (2007) Bcl-2 engineered MSCs inhibited apoptosis and improved heart function. Stem Cells 25(8):2118–2127

    Article  CAS  PubMed  Google Scholar 

  232. Nagoshi T, Matsui T, Aoyama T, Leri A, Anversa P, Li L, Ogawa W, del Monte F, Gwathmey JK, Grazette L (2005) PI3K rescues the detrimental effects of chronic Akt activation in the heart during ischemia/reperfusion injury. J Clin Invest 115(8):2128–2138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  233. Agarwal U, Ghalayini W, Dong F, Weber K, Zou Y-R, Rabbany SY, Rafii S, Penn MS (2010) Role of cardiac myocyte CXCR4 expression in development and left ventricular remodeling after acute myocardial infarction. Circ Res 107(5):667–676. doi:10.1161/circresaha.110.223289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  234. Boink GJ, Duan L, Nearing BD, Shlapakova IN, Sosunov EA, Anyukhovsky EP, Bobkov E, Kryukova Y, Ozgen N, Danilo P Jr, Cohen IS, Verrier RL, Robinson RB, Rosen MR (2013) HCN2/SkM1 gene transfer into canine left bundle branch induces stable, autonomically responsive biological pacing at physiological heart rates. J Am Coll Cardiol 61(11):1192–1201. doi:10.1016/jjacc201212031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. Hu Y-F, Dawkins JF, Cho HC, Marbán E, Cingolani E (2014) Biological pacemaker created by minimally invasive somatic reprogramming in pigs with complete heart block. Sci Transl Med 6(245):245ra294–245ra294. doi:10.1126/scitranslmed.3008681

    Article  CAS  Google Scholar 

  236. Madigan VJ, Asokan A (2016) Engineering AAV receptor footprints for gene therapy. Curr Opin Virol 18:89–96. doi:10.1016/jcoviro201605001

    Article  CAS  PubMed  Google Scholar 

  237. Asokan A (2010) Reengineered AAV vectors: old dog, new tricks. Discov Med 9(48):399–403

    PubMed  PubMed Central  Google Scholar 

  238. Zhong L, Li B, Mah CS, Govindasamy L, Agbandje-McKenna M, Cooper M, Herzog RW, Zolotukhin I, Warrington KH Jr, Weigel-Van Aken KA, Hobbs JA, Zolotukhin S, Muzyczka N, Srivastava A (2008) Next generation of adeno-associated virus 2 vectors: point mutations in tyrosines lead to high-efficiency transduction at lower doses. Proc Natl Acad Sci U S A 105(22):7827–7832. doi:10.1073/pnas0802866105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  239. Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA, Mikkelsen TS, Heckl D, Ebert BL, Root DE, Doench JG (2014) Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343(6166):84–87

    Article  CAS  PubMed  Google Scholar 

  240. Wang H, Yang H, Shivalila CS, Dawlaty MM, Cheng AW, Zhang F, Jaenisch R (2013) One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153(4):910–918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  241. Wang T, Wei JJ, Sabatini DM, Lander ES (2014) Genetic screens in human cells using the CRISPR-Cas9 system. Science 343(6166):80–84

    Article  CAS  PubMed  Google Scholar 

  242. Yang H, Wang H, Shivalila CS, Cheng AW, Shi L, Jaenisch R (2013) One-step generation of mice carrying reporter and conditional alleles by CRISPR/Cas-mediated genome engineering. Cell 154(6):1370–1379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  243. Swiech L, Heidenreich M, Banerjee A, Habib N, Li Y, Trombetta J, Sur M, Zhang F (2015) In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9. Nat Biotechnol 33(1):102–106

    Article  CAS  PubMed  Google Scholar 

  244. Zetsche B, Volz SE, Zhang F (2015) A split-Cas9 architecture for inducible genome editing and transcription modulation. Nat Biotechnol 33(2):139–142

    Article  CAS  PubMed  Google Scholar 

  245. Yan Z, Keiser NW, Song Y, Deng X, Cheng F, Qiu J, Engelhardt JF (2013) A novel chimeric adenoassociated virus 2/human bocavirus 1 parvovirus vector efficiently transduces human airway epithelia. Mol Ther 21(12):2181–2194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  246. Ran FA, Cong L, Yan WX, Scott DA, Gootenberg JS, Kriz AJ, Zetsche B, Shalem O, Wu X, Makarova KS (2015) In vivo genome editing using Staphylococcus aureus Cas9. Nature 520(7546):186–191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  247. Carroll KJ, Makarewich CA, McAnally J, Anderson DM, Zentilin L, Liu N, Giacca M, Bassel-Duby R, Olson EN (2016) A mouse model for adult cardiac-specific gene deletion with CRISPR/Cas9. Proc Natl Acad Sci 113(2):338–343

    Article  CAS  PubMed  Google Scholar 

  248. Nelson CE, Hakim CH, Ousterout DG, Thakore PI, Moreb EA, Rivera RMC, Madhavan S, Pan X, Ran FA, Yan WX (2016) In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science 351(6271):403–407

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

DS is supported by a “SERB-Fast Track Young Scientist” grant (YSS/2014/000027) from the Department of Science and Technology (DST), Government of India.

Author information

Authors and Affiliations

  1. School of Bio Sciences and Technology, VIT University, Vellore, India

    Abesh Bera

  2. Cellular and Molecular Therapeutics Laboratory, Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), VIT University, Vellore, Tamil Nadu, 632014, India

    Dwaipayan Sen

Authors
  1. Abesh Bera
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dwaipayan Sen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dwaipayan Sen.

Ethics declarations

Competing interests

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bera, A., Sen, D. Promise of adeno-associated virus as a gene therapy vector for cardiovascular diseases. Heart Fail Rev 22, 795–823 (2017). https://doi.org/10.1007/s10741-017-9622-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-017-9622-7

Keywords

Search

Navigation