Top

Published in:

01-01-2019

Biomarkers for the identification of cardiac fibroblast and myofibroblast cells

Authors: Emiri Tarbit, Indu Singh, Jason N. Peart, Roselyn B. Rose’Meyer

Published in: Heart Failure Reviews | Issue 1/2019

Abstract

Experimental research has recognized the importance of cardiac fibroblast and myofibroblast cells in heart repair and function. In a normal healthy heart, the cardiac fibroblast plays a central role in the structural, electrical, and chemical aspects within the heart. Interestingly, the transformation of cardiac fibroblast cells to cardiac myofibroblast cells is suspected to play a vital part in the development of heart failure. The ability to differentiate between the two cells types has been a challenge. Myofibroblast cells are only expressed in the stressed or failing heart, so a better understanding of cell function may identify therapies that aid repair of the damaged heart. This paper will provide an outline of what is currently known about cardiac fibroblasts and myofibroblasts, the physiological and pathological roles within the heart, and causes for the transition of fibroblasts into myoblasts. We also reviewed the potential markers available for characterizing these cells and found that there is no single-cell specific marker that delineates fibroblast or myofibroblast cells. To characterize the cells of fibroblast origin, vimentin is commonly used. Cardiac fibroblasts can be identified using discoidin domain receptor 2 (DDR2) while α-smooth muscle actin is used to distinguish myofibroblasts. A known cytokine TGF-β₁ is well established to cause the transformation of cardiac fibroblasts to myofibroblasts. This review will also discuss clinical treatments that inhibit or reduce the actions of TGF-β₁ and its contribution to cardiac fibrosis and heart failure.

Roth GA, Huffman MD, Moran AE, Feigin V, Mensah GA, Naghavi M, Murray CJ (2015) Global and regional patterns in cardiovascular mortality from 1990 to 2013. Circulation 132(17):1667–1678. https://doi.org/10.1161/circulationaha.114.008720 CrossRefPubMed

Cohn JN, Ferrari R, Sharpe N (2000) Cardiac remodeling--concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf An Int Forum Cardiac Remodeling J Am Coll Cardiol 35(3):569–582

Azevedo PS, Polegato BF, Minicucci MF, Paiva SAR, Zornoff LAM (2016) Cardiac remodeling: concepts, clinical impact. Pathophysiological Mechanisms Pharmacologic Treatment Arquivos Brasileiros de Cardiologia 106(1):62–69. https://doi.org/10.5935/abc.20160005 CrossRefPubMed

Camelliti P, Borg TK, Kohl P (2005) Structural and functional characterisation of cardiac fibroblasts. Cardiovasc Res 65(1):40–51. https://doi.org/10.1016/j.cardiores.2004.08.020 CrossRefPubMed

Souders CA, Bowers SLK, Baudino TA (2009) Cardiac Fibroblast. Renaissance Cell 105(12):1164–1176. https://doi.org/10.1161/circresaha.109.209809 CrossRef

Travers JG, Kamal FA, Robbins J, Yutzey KE, Blaxall BC (2016) Cardiac fibrosis: the fibroblast awakens. Circ Res 118(6):1021–1040. https://doi.org/10.1161/CIRCRESAHA.115.306565 CrossRefPubMedPubMedCentral

Santiago JJ, Dangerfield AL, Rattan SG, Bathe KL, Cunnington RH, Raizman JE, Bedosky KM, Freed DH, Kardami E, Dixon IM (2010) Cardiac fibroblast to myofibroblast differentiation in vivo and in vitro: expression of focal adhesion components in neonatal and adult rat ventricular myofibroblasts. Developmental Dynamics : an Official Publication Am Assoc Anatomists 239(6):1573–1584. https://doi.org/10.1002/dvdy.22280 CrossRef

Souders CA, Bowers SLK, Baudino TA (2009) Cardiac fibroblast: the renaissance cell. Circ Res 105(12):1164–1176. https://doi.org/10.1161/circresaha.109.209809 CrossRefPubMedPubMedCentral

Nag AC (1980) Study of non-muscle cells of the adult mammalian heart: a fine structural analysis and distribution. Cytobios 28(109):41–61PubMed

10.

Porter K, Turner N (2009) Cardiac fibroblasts: at the heart of myocardial remodeling. Pharmacol Therapeut 123(2):255–278. https://doi.org/10.1016/j.pharmthera.2009.05.002 CrossRef

11.

Vliegen HW, Van Der Laarse A, Cornelisse CJ, Eulderink F (1991) Myocardial changes in pressure overload-induced left ventricular hypertrophy: a study on tissue composition, polyploidization and multinucleation. European Heart J 12(4):488–494. https://doi.org/10.1093/oxfordjournals.eurheartj.a059928 CrossRef

12.

Shinde AV, Frangogiannis NG (2014) Fibroblasts in myocardial infarction: a role in inflammation and repair. J Mol Cell Cardiol 70:74–82. https://doi.org/10.1016/j.yjmcc.2013.11.015 CrossRefPubMed

13.

Baudino TA, Carver W, Giles W, Borg TK (2006) Cardiac fibroblasts: friend or foe? Am J Physiol Heart Circ Physiol 291(3):1015–1026. https://doi.org/10.1152/ajpheart.00023.2006 CrossRef

14.

MacKenna D, Summerour SR, Villarreal FJ (2000) Role of mechanical factors in modulating cardiac fibroblast function and extracellular matrix synthesis. Cardiovasc Res 46(2):257–263. https://doi.org/10.1016/S0008-6363(00)00030-4 CrossRefPubMed

15.

Zeisberg EM, Kalluri R (2010) Origins of cardiac fibroblasts. Circ Res 107(11):1304–1312. https://doi.org/10.1161/CIRCRESAHA.110.231910 CrossRefPubMedPubMedCentral

16.

Fan D, Takawale A, Lee J, Kassiri Z (2012) Cardiac fibroblasts, fibrosis and extracellular matrix remodeling in heart disease. Fibrogenesis Tissue Repair 5(1):15CrossRef

17.

Shamhart PE, Naugle JE, Olson ER, Hruska MA, Doane KJ, Meszaros JG (2007) Cardiac fibroblast migration during in vitro wound healing: the role of specific collagen substrates. FASEB J 21(6):1428–1429

18.

McSpadden LC, Kirkton RD, Bursac N (2009) Electrotonic loading of anisotropic cardiac monolayers by unexcitable cells depends on connexin type and expression level. Am J Physiol Cell Physiol 297(2):C339–C351. https://doi.org/10.1152/ajpcell.00024.2009 CrossRefPubMedPubMedCentral

19.

Muñoz V, Campbell K, Shibayama J (2008) Fibroblasts: modulating the rhythm of the heart. J Physiol 586(10):2423–2424. https://doi.org/10.1113/jphysiol.2008.153387 CrossRefPubMedPubMedCentral

20.

Yue L, Xie J, Nattel S (2011) Molecular determinants of cardiac fibroblast electrical function and therapeutic implications for atrial fibrillation. Cardiovasc Res 89(4):744–753. https://doi.org/10.1093/cvr/cvq329 CrossRefPubMed

21.

Camelliti P, Green CR, LeGrice I, Kohl P (2004) Fibroblast network in rabbit sinoatrial node: structural and functional identification of homogeneous and heterogeneous cell coupling. Circ Res 94(6):828–835. https://doi.org/10.1161/01.res.0000122382.19400.14 CrossRefPubMed

22.

Rudy Y (2004) Conductive bridges in cardiac tissue: a beneficial role or an Arrhythmogenic substrate? Circ Res 94(6):709–711. https://doi.org/10.1161/01.res.0000125647.56687.d3 CrossRefPubMed

23.

Kohl P, Camelliti P, Burton FL, Smith GL (2005) Electrical coupling of fibroblasts and myocytes: relevance for cardiac propagation. J Electrocardiol 38(4S):45–50CrossRef

24.

Swaney JS, Roth DM, Olson ER, Naugle JE, Meszaros JG, Insel PA (2005) Inhibition of cardiac myofibroblast formation and collagen synthesis by activation and overexpression of adenylyl cyclase. Proc Natl Acad Sci U S A 102(2):437–442. https://doi.org/10.1073/pnas.0408704102 CrossRefPubMed

25.

Lijnen P, Petrov V (2002) Transforming growth factor-beta 1-induced collagen production in cultures of cardiac fibroblasts is the result of the appearance of myofibroblasts. Methods Find Exp Clin Pharmacol 24(6):333–344. https://doi.org/10.1358/mf.2002.24.6.693065 CrossRefPubMed

26.

Santiago JJ, Dangerfield AL, Rattan SG, Bathe KL, Cunnington RH, Raizman JE, Bedosky KM, Freed DH, Kardami E, Dixon I (2010) Cardiac fibroblast to myofibroblast differentiation in vivo and in vitro: expression of focal adhesion components in neonatal and adult rat ventricular myofibroblasts. Dev Dyn 239(6):1573–1584. https://doi.org/10.1002/dvdy.22280 CrossRefPubMed

27.

Baum J, Duffy HS (2011) Fibroblasts and myofibroblasts: what are we talking about? J Cardiovasc Pharmacol 57(4):376–379. https://doi.org/10.1097/FJC.0b013e3182116e39 CrossRefPubMedPubMedCentral

28.

Roy SG, Nozaki Y, Phan SH (2001) Regulation of α-smooth muscle actin gene expression in myofibroblast differentiation from rat lung fibroblasts. Int J Biochem Cell Biol 33(7):723–734. https://doi.org/10.1016/S1357-2725(01)00041-3 CrossRefPubMed

29.

Ehrlich HP, Allison GM, Leggett M (2006) The myofibroblast, cadherin, alpha smooth muscle actin and the collagen effect. Cell Biochem Funct 24(1):63–70. https://doi.org/10.1002/cbf.1188 CrossRefPubMed

30.

Nakaya M, Watari K, Tajima M, Nakaya T, Matsuda S, Ohara H, Nishihara H, Yamaguchi H, Hashimoto A, Nishida M, Nagasaka A, Horii Y, Ono H, Iribe G, Inoue R, Tsuda M, Inoue K, Tanaka A, Kuroda M, Nagata S, Kurose H (2017) Cardiac myofibroblast engulfment of dead cells facilitates recovery after myocardial infarction. J Clin Invest 127(1):383–401. https://doi.org/10.1172/JCI83822 CrossRefPubMed

31.

Bergmann MW (2010) WNT signaling in adult cardiac hypertrophy and remodeling lessons learned from cardiac development. Circ Res 107(10):1198–1208. https://doi.org/10.1161/CIRCRESAHA.110.223768 CrossRefPubMed

32.

MacLean J, Pasumarthi KB (2014) Signaling mechanisms regulating fibroblast activation, phenoconversion and fibrosis in the heart. Indian J Biochem Biophys 51(6):476–482PubMed

33.

Liu S, Xu SW, Kennedy L, Pala D, Chen Y, Eastwood M, Carter DE, Black CM, Abraham DJ, Leask A (2007) FAK is required for TGFbeta-induced JNK phosphorylation in fibroblasts: implications for acquisition of a matrix-remodeling phenotype. Mol Biol Cell 18(6):2169–2178. https://doi.org/10.1091/mbc.E06-12-1121 CrossRefPubMedPubMedCentral

34.

Komiya Y, Habas R (2008) Wnt signal transduction pathways. Organogenesis 4(2):68–75. https://doi.org/10.4161/org.4.2.5851 CrossRefPubMedPubMedCentral

35.

Cohen ED, Tian Y, Morrisey EE (2008) Wnt signaling: an essential regulator of cardiovascular differentiation, morphogenesis and progenitor self-renewal. Development 135(5):789–798. https://doi.org/10.1242/dev.016865 CrossRefPubMed

36.

Dawson K, Aflaki M, Nattel S (2013) Role of the Wnt-frizzled system in cardiac pathophysiology: a rapidly developing, poorly understood area with enormous potential. J Physiol 591(Pt 6):1409–1432. https://doi.org/10.1113/jphysiol.2012.235382 CrossRefPubMed

37.

Zhang D, Gaussin V, Taffet GE, Belaguli NS, Yamada M, Schwartz RJ, Michael LH, Overbeek PA, Schneider MD (2000) TAK1 is activated in the myocardium after pressure overload and is sufficient to provoke heart failure in transgenic mice. Nat Med 6(5):556–563. https://doi.org/10.1038/75037 CrossRefPubMed

38.

Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat M-L, Gabbiani G (2007) The Myofibroblast: one function, multiple origins. Am J Pathol 170(6):1807–1816. https://doi.org/10.2353/ajpath.2007.070112 CrossRefPubMedPubMedCentral

39.

Dobaczewski M, Chen W, Frangogiannis NG (2010) Transforming growth factor (TGF)-β signaling in cardiac remodeling. J Mol Cell Cardiol 51(4):600–606. https://doi.org/10.1016/j.yjmcc.2010.10.033 CrossRefPubMedPubMedCentral

40.

Shi M, Zhu J, Wang R, Chen X, Mi L, Walz T, Springer TA (2011) Latent TGF-β structure and activation. Nature 474(7351):343–349. https://doi.org/10.1038/nature10152 CrossRefPubMedPubMedCentral

41.

Blakytny R, Ludlow A, Martin G, Ireland G, Lund LR, Ferguson M, Brunner G (2004) Latent TGF-β1 activation by platelets. J Cell Physiol 199(1):67–76. https://doi.org/10.1002/jcp.10454 CrossRefPubMed

42.

Taylor AW (2009) Review of the activation of TGF-beta in immunity. J Leukoc Biol 85(1):29–33. https://doi.org/10.1189/jlb.0708415 CrossRefPubMed

43.

Folger PA, Zekaria D, Grotendorst G, Masur SK (2001) Transforming growth factor-beta-stimulated connective tissue growth factor expression during corneal myofibroblast differentiation. Invest Ophthalmol Vis Sci 42(11):2534–2541PubMed

44.

Hinz B (2007) Formation and function of the Myofibroblast during tissue repair. J Investig Dermatol 127(3):526–537. https://doi.org/10.1038/sj.jid.5700613 CrossRefPubMed

45.

Henderson NC, Mackinnon AC, Farnworth SL, Poirier F, Russo FP, Iredale JP, Haslett C, Simpson KJ, Sethi T (2006) Galectin-3 regulates myofibroblast activation and hepatic fibrosis. Proc Natl Acad Sci U S A 103(13):5060–5065. https://doi.org/10.1073/pnas.0511167103 CrossRefPubMedPubMedCentral

46.

Shephard P, Martin G, Smola-Hess S, Brunner G (2004) Myofibroblast differentiation is induced in keratinocyte-fibroblast co-cultures and is antagonistically regulated by endogenous transforming growth factor-β and Interleukin-1. Am J Pathol 164(6):2055–2066. https://doi.org/10.1016/S0002-9440(10)63764-9 CrossRefPubMedPubMedCentral

47.

Gallucci RM, Lee EG, Tomasek JJ (2006) IL-6 modulates alpha-smooth muscle actin expression in dermal fibroblasts from IL-6-deficient mice. J Investigative Dermatology 126(3):561–568. https://doi.org/10.1038/sj.jid.5700109 CrossRef

48.

Bujak M, Frangogiannis NG (2007) The role of TGF-beta signaling in myocardial infarction and cardiac remodeling. Cardiovasc Res 74(2):184–195. https://doi.org/10.1016/j.cardiores.2006.10.002 CrossRefPubMed

49.

Li P, Wang D, Lucas J, Oparil S, Xing D, Cao X, Novak L, Renfrow MB, Chen Y-F (2008) Atrial natriuretic peptide inhibits transforming growth factor –induced smad signaling and myofibroblast transformation in mouse cardiac fibroblasts. Circ Res 102(2):185–192. https://doi.org/10.1161/CIRCRESAHA.107.157677 CrossRefPubMed

50.

Vivar R, Humeres C, Ayala P, Olmedo I, Catalán M, García L, Lavandero S, Díaz-Araya G (2013) TGF-β1 prevents simulated ischemia/reperfusion-induced cardiac fibroblast apoptosis by activation of both canonical and non-canonical signaling pathways. Biochim Biophys Acta (BBA) - Mol Basis Dis 1832(6):754–762. https://doi.org/10.1016/j.bbadis.2013.02.004 CrossRef

51.

Phan SH (2008) Biology of fibroblasts and myofibroblasts. Proc Am Thorac Soc 5(3):334–337. https://doi.org/10.1513/pats.200708-146dr CrossRefPubMedPubMedCentral

52.

Talman V, Ruskoaho H (2016) Cardiac fibrosis in myocardial infarction—from repair and remodeling to regeneration. Cell Tissue Res 365(3):563–581. https://doi.org/10.1007/s00441-016-2431-9 CrossRefPubMedPubMedCentral

53.

Aurora AB, Porrello ER, Tan W, Mahmoud AI, Hill JA, Bassel-Duby R, Sadek HA, Olson EN (2014) Macrophages are required for neonatal heart regeneration. J Clin Investig 124(3):1382–1392. https://doi.org/10.1172/jci72181 CrossRefPubMed

54.

Saxena A, Chen W, Su Y, Rai V, Uche OU, Li N, Frangogiannis NG (2013) IL-1 induces proinflammatory leukocyte infiltration and regulates fibroblast phenotype in the infarcted myocardium. J Immunology (Baltimore, Md : 1950) 191(9):4838–4848. https://doi.org/10.4049/jimmunol.1300725 CrossRef

55.

Frangogiannis NG (2014) The inflammatory response in myocardial injury, repair, and remodelling. Nat Rev Cardiol 11(5):255–265. https://doi.org/10.1038/nrcardio.2014.28 CrossRefPubMedPubMedCentral

56.

van den Borne SWM, Diez J, Blankesteijn WM, Verjans J, Hofstra L, Narula J (2010) Myocardial remodeling after infarction: the role of myofibroblasts. Nat Rev Cardiol 7(1):30–37CrossRef

57.

Van Linthout S, Miteva K, Tschöpe C (2014) Crosstalk between fibroblasts and inflammatory cells. Cardiovasc Res 102(2):258–269. https://doi.org/10.1093/cvr/cvu062 CrossRefPubMed

58.

Bai J, Zhang N, Hua Y, Wang B, Ling L, Ferro A, Xu B (2013) Metformin inhibits angiotensin II-induced differentiation of cardiac fibroblasts into Myofibroblasts. PLoS One 8(9):e72120. https://doi.org/10.1371/journal.pone.0072120 CrossRefPubMedPubMedCentral

59.

Cheng T-HH, Cheng P-YY, Shih N-LL, Chen I-BB, Wang DL, Chen J-JJ (2003) Involvement of reactive oxygen species in angiotensin II-induced endothelin-1 gene expression in rat cardiac fibroblasts. J Am Coll Cardiol 42(10):1845–1854CrossRef

60.

Lijnen PJ, van Pelt JF, Fagard RH (2012) Stimulation of reactive oxygen species and collagen synthesis by angiotensin II in cardiac fibroblasts. Cardiovasc Ther 30(1):8–e8. https://doi.org/10.1111/j.1755-5922.2010.00205.x CrossRef

61.

Jiang F, Liu G-S, Dusting GJ, Chan EC (2014) NADPH oxidase-dependent redox signaling in TGF-β-mediated fibrotic responses. Redox Biol 2:267–272. https://doi.org/10.1016/j.redox.2014.01.012 CrossRefPubMedPubMedCentral

62.

Thannickal VJ (2010) Aging, antagonistic pleiotropy and fibrotic disease. Int J Biochem Cell Biol 42(9):1398–1400. https://doi.org/10.1016/j.biocel.2010.05.010 CrossRefPubMedPubMedCentral

63.

Murphy AM, Wong AL, Bezuhly M (2015) Modulation of angiotensin II signaling in the prevention of fibrosis. Fibrogenesis Tissue Repair 8(1):7. https://doi.org/10.1186/s13069-015-0023-z CrossRefPubMedPubMedCentral

64.

Wang J, Chen H, Seth A, McCulloch CA (2003) Mechanical force regulation of myofibroblast differentiation in cardiac fibroblasts. Am J Physiol Heart Circ Physiol 285(5):1871–1881. https://doi.org/10.1152/ajpheart.00387.2003 CrossRef

65.

Gazoti Debessa CR, Mesiano Maifrino LB, Rodrigues de Souza R (2001) Age related changes of the collagen network of the human heart. Mech Ageing Dev 122(10):1049–1058. https://doi.org/10.1016/S0047-6374(01)00238-X CrossRefPubMed

66.

Cieslik KA, Trial J, Crawford JR, Taffet GE, Entman ML (2014) Adverse fibrosis in the aging heart depends on signaling between myeloid and mesenchymal cells; role of inflammatory fibroblasts. J Mol Cell Cardiol 0:56–63. https://doi.org/10.1016/j.yjmcc.2013.10.017 CrossRef

67.

Chiao YA, Ramirez TA, Zamilpa R, Okoronkwo SM, Dai Q, Zhang J, Jin Y-F, Lindsey ML (2012) Matrix metalloproteinase-9 deletion attenuates myocardial fibrosis and diastolic dysfunction in ageing mice. Cardiovasc Res 96(3):444–455. https://doi.org/10.1093/cvr/cvs275 CrossRefPubMedPubMedCentral

68.

Segers VFM, Lee RT (2010) Protein therapeutics for cardiac regeneration after myocardial infarction. J Cardiovasc Transl Res 3(5):469–477. https://doi.org/10.1007/s12265-010-9207-5 CrossRefPubMedPubMedCentral

69.

Strait JB, Lakatta EG (2012) Aging-associated cardiovascular changes and their relationship to heart failure. Heart Fail Clin 8(1):143–164. https://doi.org/10.1016/j.hfc.2011.08.011 CrossRefPubMedPubMedCentral

70.

Masur SK, Dewal HS, Dinh TT, Erenburg I, Petridou S (1996) Myofibroblasts differentiate from fibroblasts when plated at low density. Proc Natl Acad Sci 93(9):4219–4223. https://doi.org/10.1073/pnas.93.9.4219 CrossRefPubMed

71.

Chang HY, Chi J-T, Dudoit S, Bondre C, van de Rijn M, Botstein D, Brown PO (2002) Diversity, topographic differentiation, and positional memory in human fibroblasts. Proc Natl Acad Sci 99(20):12877–12882. https://doi.org/10.1073/pnas.162488599 CrossRefPubMed

72.

Moore-Morris T, Guimarães-Camboa N, Yutzey KE, Pucéat M, Evans SM (2015) Cardiac fibroblasts: from development to heart failure. J Molecular Medicine (Berlin, Germany) 93(8):823–830. https://doi.org/10.1007/s00109-015-1314-y CrossRef

73.

Doppler SA, Carvalho C, Lahm H, Deutsch M-A, Dreßen M, Puluca N, Lange R, Krane M (2017) Cardiac fibroblasts: more than mechanical support. J Thoracic Disease 9:S36–S51CrossRef

74.

Ivey MJ, Tallquist MD (2016) Defining the cardiac fibroblast. Circ J 80(11):2269–2276. https://doi.org/10.1253/circj.CJ-16-1003 CrossRefPubMedPubMedCentral

75.

Turner NA, Porter KE (2013) Function and fate of myofibroblasts after myocardial infarction. Fibrogenesis Tissue Repair 6(1):5. https://doi.org/10.1186/1755-1536-6-5 CrossRefPubMedPubMedCentral

76.

Zahradka P (2008) Novel role for osteopontin in cardiac fibrosis. Circ Res 102(3):270–272. https://doi.org/10.1161/circresaha.107.170555 CrossRefPubMed

77.

Tamaoki M, Imanaka-Yoshida K, Yokoyama K, Nishioka T, Inada H, Hiroe M, Sakakura T, Yoshida T (2005) Tenascin-C regulates recruitment of Myofibroblasts during tissue repair after myocardial injury. Am J Pathol 167(1):71–80CrossRef

78.

Shimazaki M, Nakamura K, Kii I, Kashima T, Amizuka N, Li M, Saito M, Fukuda K, Nishiyama T, Kitajima S, Saga Y, Fukayama M, Sata M, Kudo A (2008) Periostin is essential for cardiac healingafter acute myocardial infarction. J Exp Med 205(2):295–303. https://doi.org/10.1084/jem.20071297 CrossRefPubMedPubMedCentral

79.

Zhao S, Wu H, Xia W, Chen X, Zhu S, Zhang S, Shao Y, Ma W, Yang D, Zhang J (2014) Periostin expression is upregulated and associated with myocardial fibrosis in human failing hearts. J Cardiol 63(5):373–378. https://doi.org/10.1016/j.jjcc.2013.09.013 CrossRefPubMed

80.

Snider P, Standley KN, Wang J, Azhar M, Doetschman T, Conway SJ (2009) Origin of cardiac fibroblasts and the role of periostin. Circ Res 105(10):934–947. https://doi.org/10.1161/circresaha.109.201400 CrossRefPubMedPubMedCentral

81.

Kanisicak O, Khalil H, Ivey MJ, Karch J, Maliken BD, Correll RN, Brody MJ, J Lin SC, Aronow BJ, Tallquist MD, Molkentin JD (2016) Genetic lineage tracing defines myofibroblast origin and function in the injured heart. Nature Communications 7:12260. https://doi.org/10.1038/ncomms12260 https://www.nature.com/articles/ncomms12260#supplementary-information CrossRefPubMedPubMedCentral

83.

Leslie KO, Taatjes DJ, Schwarz J, vonTurkovich M, Low RB (1991) Cardiac myofibroblasts express alpha smooth muscle actin during right ventricular pressure overload in the rabbit. Am J Pathol 139(1):207–216PubMedPubMedCentral

84.

Ma Y, Iyer RP, Jung M, Czubryt MP, Lindsey ML (2017) Cardiac fibroblast activation post-myocardial infarction: current knowledge gaps. Trends Pharmacol Sci 38(5):448–458. https://doi.org/10.1016/j.tips.2017.03.001 CrossRefPubMedPubMedCentral

85.

Chen W, Frangogiannis NG (2013) Fibroblasts in post-infarction inflammation and cardiac repair. Biochim Biophys Acta 1833(4):945–953. https://doi.org/10.1016/j.bbamcr.2012.08.023 CrossRefPubMed

86.

Villarreal FJ, Kim NN, Ungab GD, Printz MP, Dillmann WH (1993) Identification of functional angiotensin II receptors on rat cardiac fibroblasts. Circulation 88(6):2849–2861CrossRef

87.

Bursac N (2014) Cardiac fibroblasts in pressure overload hypertrophy: the enemy within? J Clin Investig 124(7):2850–2853. https://doi.org/10.1172/jci76628 CrossRefPubMed

88.

Moore-Morris T, Guimarães-Camboa N, Banerjee I, Zambon AC, Kisseleva T, Velayoudon A, Stallcup WB, Gu Y, Dalton ND, Cedenilla M, Gomez-Amaro R, Zhou B, Brenner DA, Peterson KL, Chen J, Evans SM (2014) Resident fibroblast lineages mediate pressure overload–induced cardiac fibrosis. J Clin Invest 124(7):2921–2934. https://doi.org/10.1172/JCI74783 CrossRefPubMedPubMedCentral

89.

Ashizawa N, Graf K, Do YS, Nunohiro T, Giachelli CM, Meehan WP, Tuan TL, Hsueh WA (1996) Osteopontin is produced by rat cardiac fibroblasts and mediates a(II)-induced DNA synthesis and collagen gel contraction. J Clin Investig 98(10):2218–2227CrossRef

90.

Snider P, Standley KN, Wang J, Azhar M, Doetschman T, Conway SJ (2009) Origin of cardiac fibroblasts and the role of Periostin. Circ Res 105(10):934–947. https://doi.org/10.1161/CIRCRESAHA.109.201400 CrossRefPubMedPubMedCentral

91.

Donovan J, Shiwen X, Norman J, Abraham D (2013) Platelet-derived growth factor alpha and beta receptors have overlapping functional activities towards fibroblasts. Fibrogenesis Tissue Repair 6:10–10. https://doi.org/10.1186/1755-1536-6-10 CrossRefPubMedPubMedCentral

92.

Sun W, Zhang H, Guo J, Zhang X, Zhang L, Li C, Zhang L (2016) Comparison of the efficacy and safety of different ACE inhibitors in patients with chronic heart failure: a PRISMA-compliant network meta-analysis. Medicine 95(6):e2554. https://doi.org/10.1097/MD.0000000000002554 CrossRefPubMedPubMedCentral

93.

Ellmers LJ, Scott NJ, Medicherla S, Pilbrow AP, Bridgman PG, Yandle TG, Richards AM, Protter AA, Cameron VA (2008) Transforming growth factor-beta blockade down-regulates the renin-angiotensin system and modifies cardiac remodeling after myocardial infarction. Endocrinology 149(11):5828–5834. https://doi.org/10.1210/en.2008-0165 CrossRefPubMed

94.

Li L, Bounds KR, Chatterjee P, Gupta S (2017) MicroRNA-130a, a potential Antifibrotic target in cardiac fibrosis. J Am Heart Assoc 6(11):e006763. https://doi.org/10.1161/jaha.117.006763 CrossRefPubMedPubMedCentral

95.

Mann DL, McMurray JJ, Packer M, Swedberg K, Borer JS, Colucci WS, Djian J, Drexler H, Feldman A, Kober L, Krum H, Liu P, Nieminen M, Tavazzi L, van Veldhuisen DJ, Waldenstrom A, Warren M, Westheim A, Zannad F, Fleming T (2004) Targeted anticytokine therapy in patients with chronic heart failure: results of the randomized Etanercept worldwide evaluation (RENEWAL). Circulation 109(13):1594–1602. https://doi.org/10.1161/01.cir.0000124490.27666.b2 CrossRefPubMed

96.

Brilla CG, Funck RC, Rupp H (2000) Lisinopril-mediated regression of myocardial fibrosis in patients with hypertensive heart disease. Circulation 102(12):1388–1393CrossRef

97.

Diez J, Querejeta R, Lopez B, Gonzalez A, Larman M, Martinez Ubago JL (2002) Losartan-dependent regression of myocardial fibrosis is associated with reduction of left ventricular chamber stiffness in hypertensive patients. Circulation 105(21):2512–2517CrossRef

98.

Shimada YJ, Passeri JJ, Baggish AL, O’Callaghan C, Lowry PA, Yannekis G, Abbara S, Ghoshhajra BB, Rothman RD, Ho CY, Januzzi JL, Seidman CE, Fifer MA (2013) Effects of losartan on left ventricular hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy. JACC Heart failure 1(6):480–487. https://doi.org/10.1016/j.jchf.2013.09.001 CrossRefPubMedPubMedCentral

99.

Mendell JR, Sahenk Z, Al-Zaidy S, Rodino-Klapac LR, Lowes LP, Alfano LN, Berry K, Miller N, Yalvac M, Dvorchik I, Moore-Clingenpeel M, Flanigan KM, Church K, Shontz K, Curry C, Lewis S, McColly M, Hogan MJ, Kaspar BK (2017) Follistatin gene therapy for sporadic inclusion body myositis improves functional outcomes. Mol Ther 25(4):870–879. https://doi.org/10.1016/j.ymthe.2017.02.015 CrossRefPubMedPubMedCentral

100.

Martin J, Kelly DJ, Mifsud SA, Zhang Y, Cox AJ, See F, Krum H, Wilkinson-Berka J, Gilbert RE (2005) Tranilast attenuates cardiac matrix deposition in experimental diabetes: role of transforming growth factor-β. Cardiovasc Res 65(3):694–701. https://doi.org/10.1016/j.cardiores.2004.10.041 CrossRefPubMed

101.

Hocher B, Godes M, Olivier J, Weil J, Eschenhagen T, Slowinski T, Neumayer HH, Bauer C, Paul M, Pinto YM (2002) Inhibition of left ventricular fibrosis by tranilast in rats with renovascular hypertension. J Hypertens 20(4):745–751CrossRef

102.

Hager M, Pedersen CC, Larsen MT, Andersen MK, Hother C, Gronbaek K, Jarmer H, Borregaard N, Cowland JB (2011) MicroRNA-130a-mediated down-regulation of Smad4 contributes to reduced sensitivity to TGF-beta1 stimulation in granulocytic precursors. Blood 118(25):6649–6659. https://doi.org/10.1182/blood-2011-03-339978 CrossRefPubMed

103.

Tijsen AJ, van der Made I, van den Hoogenhof MM, Wijnen WJ, van Deel ED, de Groot NE, Alekseev S, Fluiter K, Schroen B, Goumans M-J, van der Velden J, Duncker DJ, Pinto YM, Creemers EE (2014) The microRNA-15 family inhibits the TGFβ-pathway in the heart. Cardiovasc Res 104(1):61–71. https://doi.org/10.1093/cvr/cvu184 CrossRefPubMed

104.

Giam B, Chu PY, Kuruppu S, Smith AI, Horlock D, Kiriazis H, Du XJ, Kaye DM, Rajapakse NW (2016) N-acetylcysteine attenuates the development of cardiac fibrosis and remodeling in a mouse model of heart failure. Physiological Reports 4(7):e12757. https://doi.org/10.14814/phy2.12757 CrossRefPubMedPubMedCentral

Title: Biomarkers for the identification of cardiac fibroblast and myofibroblast cells
Authors: Emiri Tarbit
Indu Singh
Jason N. Peart
Roselyn B. Rose’Meyer
Publication date: 01-01-2019
Publisher: Springer US
Published in: Heart Failure Reviews / Issue 1/2019
Print ISSN: 1382-4147
Electronic ISSN: 1573-7322
DOI: https://doi.org/10.1007/s10741-018-9720-1

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The STEP trials

Springer Medicine

Biomarkers for the identification of cardiac fibroblast and myofibroblast cells

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2019

Cardio-oncology: a new and developing sector of research and therapy in the field of cardiology

Flow-mediated dilation and heart failure: a review with implications to physical rehabilitation

Lanosteryl triterpenes from Protorhus longifolia as a cardioprotective agent: a mini review

Intercalated discs: cellular adhesion and signaling in heart health and diseases

Understanding non-response to cardiac resynchronisation therapy: common problems and potential solutions

Diagnostic and prognostic role of cardiac magnetic resonance in acute myocarditis

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page