Skip to main content
SpringerLink
Log in

Calcific Aortic Valve Disease: Part 2—Morphomechanical Abnormalities, Gene Reexpression, and Gender Effects on Ventricular Hypertrophy and Its Reversibility

  • Review
  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

In part 1, we considered cytomolecular mechanisms underlying calcific aortic valve disease (CAVD), hemodynamics, and adaptive feedbacks controlling pathological left ventricular hypertrophy provoked by ensuing aortic valvular stenosis (AVS). In part 2, we survey diverse signal transduction pathways that precede cellular/molecular mechanisms controlling hypertrophic gene expression by activation of specific transcription factors that induce sarcomere replication in-parallel. Such signaling pathways represent potential targets for therapeutic intervention and prevention of decompensation/failure. Hypertrophy provoking signals, in the form of dynamic stresses and ligand/effector molecules that bind to specific receptors to initiate the hypertrophy, are transcribed across the sarcolemma by several second messengers. They comprise intricate feedback mechanisms involving gene network cascades, specific signaling molecules encompassing G protein-coupled receptors and mechanotransducers, and myocardial stresses. Future multidisciplinary studies will characterize the adaptive/maladaptive nature of the AVS-induced hypertrophy, its gender- and individual patient-dependent peculiarities, and its response to surgical/medical interventions. They will herald more effective, precision medicine treatments.

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
Fig. 4

Similar content being viewed by others

References

  1. Pasipoularides, A. (2016). Calcific aortic valve disease: part 1—molecular pathogenetic aspects, hemodynamics and adaptive feedbacks. Journal of Cardiovascular Translational Research, 9, 102–118.

  2. Krishnamurthy, V. K., Godby, R. C., Liu, G. R., et al. (2014). Review of molecular and mechanical interactions in the aortic valve and aorta: implications for the shared pathogenesis of aortic valve disease and aortopathy. Journal of Cardiovascular Translational Research, 7, 823–46.

    Article  PubMed  Google Scholar 

  3. Pasipoularides, A. (2010). Heart's vortex: intracardiac blood flow phenomena. Shelton: People's Medical Publishing House. 960 p.

    Google Scholar 

  4. Osler, W. (1892). The principles and practice of medicine: designed for the use of practitioners and students of medicine. New York: D. Appleton.

    Google Scholar 

  5. Pasipoularides, A. (2015). Mechanotransduction mechanisms for intraventricular diastolic vortex forces and myocardial deformations: part 1. Journal of Cardiovascular Translational Research, 8, 76–87.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Pasipoularides, A. (2015). Mechanotransduction mechanisms for intraventricular diastolic vortex forces and myocardial deformations: part 2. Journal of Cardiovascular Translational Research, 8, 293–318.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Barbato, E., Barton, P. J., Bartunek, J., Huber, S., Ibanez, B., Judge, D. P., Lara-Pezzi, E., Stolen, C. M., Taylor, A., & Hall, J. L. (2015). Review and updates in regenerative and personalized medicine, preclinical animal models, and clinical care in cardiovascular medicine. Journal of Cardiovascular Translational Research, 8, 466–74.

    Article  PubMed  Google Scholar 

  8. Leri, A., Kajstura, J., & Anversa, P. (2011). Role of cardiac stem cells in cardiac pathophysiology: a paradigm shift in human myocardial biology. Circulation Research, 109, 941–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ellison, G. M., Nadal-Ginard, B., & Torella, D. (2012). Optimizing cardiac repair and regeneration through activation of the endogenous cardiac stem cell compartment. Journal of Cardiovascular Translational Research, 5, 667–77.

    Article  PubMed  Google Scholar 

  10. Marketou, M. E., Parthenakis, F., & Vardas, P. E. (2016). Pathological left ventricular hypertrophy and stem cells: current evidence and new perspectives. Stem Cells International, 2016, 5720758.

    Article  PubMed  Google Scholar 

  11. Urbanek, K., Quaini, F., Tasca, G., et al. (2003). Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy. Proceedings of the National Academy of Sciences of the United States of America, 100, 10440–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Artavanis-Tsakonas, S., Rand, M. D., & Lake, R. J. (1999). Notch signaling: cell fate control and signal integration in development. Science, 284, 770–6.

    Article  CAS  PubMed  Google Scholar 

  13. Mumm, J. S., & Kopan, R. (2000). Notch signaling: from the outside in. Developmental Biology, 228, 151–65.

    Article  CAS  PubMed  Google Scholar 

  14. Bray, S. J. (2006). Notch signalling: a simple pathway becomes complex. Nature Reviews. Molecular Cell Biology, 7, 678–89.

    Article  CAS  PubMed  Google Scholar 

  15. Gude, N., & Sussman, M. (2012). Notch signaling and cardiac repair. Journal of Molecular and Cellular Cardiology, 52, 1226–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Elmadhun, N. Y., Sabe, A. A., Lassaletta, A. D., et al. (2014). Metabolic syndrome impairs notch signaling and promotes apoptosis in chronically ischemic myocardium. Journal of Thoracic and Cardiovascular Surgery, 148, 1048–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Nemir, M., & Pedrazzini, T. (2008). Functional role of Notch signaling in the developing and postnatal heart. Journal of Molecular and Cellular Cardiology, 45, 495–504.

    Article  CAS  PubMed  Google Scholar 

  18. Barry, S. P., Davidson, S. M., & Townsend, P. A. (2008). Molecular regulation of cardiac hypertrophy. International Journal of Biochemistry and Cell Biology, 40, 2023–39.

    Article  CAS  PubMed  Google Scholar 

  19. Pilegaard, H., Saltin, B., & Neufer, P. D. (2003). Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle. Journal of Physiology, 546(3), 851–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Keeling, P.J., & Archibald, J.M. Organelle evolution: what’s in a name? Current Biology, 18, 345–347.

  21. Blackstone, N. W. (2013). Evolution and cell physiology. 2. The evolution of cell signaling: from mitochondria to Metazoa. American Journal of Physiology. Cell Physiology, 305, C909–15.

    Article  CAS  PubMed  Google Scholar 

  22. Vega, R. B., Horton, J. L., & Kelly, D. P. (2015). Maintaining ancient organelles: mitochondrial biogenesis and maturation. Circulation Research, 116, 1820–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chacinska, A., Koehler, C. M., Milenkovic, D., Lithgow, T., & Pfanner, N. (2009). Importing mitochondrial proteins: machineries and mechanisms. Cell, 138, 628–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Shokolenko, I., Venediktova, N., Bochkareva, A., Wilson, G. L., & Alexeyev, M. F. (2009). Oxidative stress induces degradation of mitochondrial DNA. Nucleic Acids Research, 37, 2539–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Maulik, S. K., & Kumar, S. (2012). Oxidative stress and cardiac hypertrophy: a review. Toxicology Mechanisms and Methods, 22, 359–66.

    Article  CAS  PubMed  Google Scholar 

  26. van der Bliek, A. M., Shen, Q., & Kawajiri, S. (2013). Mechanisms of mitochondrial fission and fusion. Cold Spring Harbor Perspectives in Biology, 5, a011072.

    PubMed  PubMed Central  Google Scholar 

  27. Twig, G., Elorza, A., Molina, A. J. A., et al. (2008). Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. The EMBO Journal, 27, 433–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sciarretta, S., Zhai, P., Volpe, M., & Sadoshima, J. (2012). Pharmacological modulation of autophagy during cardiac stress. Journal of Cardiovascular Pharmacology, 60, 235–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Carafoli, E. (1797). The fateful encounter of mitochondria with calcium: how did it happen? Biochimica et Biophysica Acta, 2010, 595–606.

    Google Scholar 

  30. Winslow, R. L., Walker, M. A., & Greenstein, J. L. (2016). Modeling calcium regulation of contraction, energetics, signaling, and transcription in the cardiac myocyte. WIREs Systems Biology and Medicine, 8, 37–67.

    Article  CAS  PubMed  Google Scholar 

  31. Abel, E. D., & Doenst, T. (2011). Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy. Cardiovascular Research, 90, 234–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Droge, W. (2002). Free radicals in the physiological control of cell function. Physiological Reviews, 82, 47–95.

    Article  CAS  PubMed  Google Scholar 

  33. Lee, H. C., & Wei, Y. H. (2000). Mitochondrial role in life and death of the cell. Journal of Biomedical Science, 7, 2–15.

    Article  CAS  PubMed  Google Scholar 

  34. Levy, D., Salomon, M., D’Agostino, R. B., Belanger, A. J., & Kannel, W. B. (1994). Prognostic implications of baseline electrocardiographic features and their serial changes in subjects with left ventricular hypertrophy. Circulation, 90, 1786–93.

    Article  CAS  PubMed  Google Scholar 

  35. Condorelli, G., Morisco, C., Stassi, G., et al. (1999). Increased cardiomyocyte apoptosis and changes in proapoptotic and antiapoptotic genes bax and bcl-2 during left ventricular adaptations to chronic pressure overload in the rat. Circulation, 99, 3071–8.

    Article  CAS  PubMed  Google Scholar 

  36. Spence, A. L., Naylor, L. H., Carter, H. H., et al. (2011). A prospective randomised longitudinal MRI study of left ventricular adaptation to endurance and resistance exercise training in humans. Journal of Physiology, 589, 5443–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Komamura, K., Shannon, R. P., Pasipoularides, A., Ihara, T., Lader, A. S., Patrick, T. A., Bishop, S. P., & Vatner, S. F. (1992). Alterations in left ventricular diastolic function in conscious dogs with pacing-induced heart failure. Journal of Clinical Investigation, 89, 1825–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. DeBosch, B., Treskov, I., Lupu, T. S., et al. (2006). Akt1 is required for physiological cardiac growth. Circulation, 113, 2097–104.

    Article  CAS  PubMed  Google Scholar 

  39. Dom, G. W., II, & Force, T. (2005). Protein kinase cascades in the regulation of cardiac hypertrophy. Journal of Clinical Investigation, 115, 527–37.

    Article  Google Scholar 

  40. Molkentin, J. D. (2004). Calcineurin–NFAT signaling regulates the cardiac hypertrophic response in coordination with the MAPKs. Cardiovascular Research, 63, 467–75.

    Article  CAS  PubMed  Google Scholar 

  41. Taegtmeyer, H., Sen, S., & Vela, D. (2010). Return to the fetal gene program. Annals of the New York Academy of Sciences, 1188(1), 191–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Maillet, M., van Berlo, J. H., & Molkentin, J. D. (2013). Molecular basis of physiological heart growth: fundamental concepts and new players. Nature Reviews. Molecular Cell Biology, 14, 38–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Martin, D. E., Soulard, A., & Hall, M. N. (2004). TOR regulates ribosomal protein gene expression via PKA and the Forkhead transcription factor FHL1. Cell, 119, 969–79.

    Article  CAS  PubMed  Google Scholar 

  44. Leri, A., Claudio, P. P., Li, Q., et al. (1998). Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases the Bcl- 2-to-Bax protein ratio in the cell. Journal of Clinical Investigation, 101, 1326–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Dweck, M. R., Boon, N. A., & Newby, D. E. (2012). Calcific aortic stenosis: a disease of the valve and the myocardium. Journal of the American College of Cardiology, 60, 1854–63.

    Article  PubMed  Google Scholar 

  46. Ricci, J. E., Munoz-Pinedo, C., Fitzgerald, P., et al. (2004). Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain. Cell, 117, 773–86.

    Article  CAS  PubMed  Google Scholar 

  47. Porrello, E. R., D’Amore, A., Curl, C. L., et al. (2009). Angiotensin II type 2 receptor antagonizes angiotensin II type 1 receptor-mediated cardiomyocyte autophagy. Hypertension, 53, 1032–40.

    Article  CAS  PubMed  Google Scholar 

  48. Dai, D. F., & Rabinovitch, P. (2011). Mitochondrial oxidative stress mediates induction of autophagy and hypertrophy in angiotensin-II treated mouse hearts. Autophagy, 7, 917–8.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Liu, S., Chen, S., Li, M., et al. (2016). Autophagy activation attenuates angiotensin II-induced cardiac fibrosis. Archives of Biochemistry and Biophysics, 590, 37–47.

    Article  CAS  PubMed  Google Scholar 

  50. Soonpaa, M. H., Kim, K. K., Pajak, L., Franklin, M., & Field, L. J. (1996). Cardiomyocyte DNA synthesis and binucleation during murine development. American Journal of Physiology. Heart and Circulatory Physiology, 271, H2183–9.

    CAS  Google Scholar 

  51. Woodcock, E. A., & Matkovich, S. J. (2005). Cardiomyocytes structure, function and associated pathologies. International Journal of Biochemistry and Cell Biology, 37, 1746–51.

    Article  CAS  PubMed  Google Scholar 

  52. Miyata, S., Minobe, W., Bristow, M. R., & Leinwand, L. A. (2000). Myosin heavy chain isoform expression in the failing and nonfailing human heart. Circulation Research, 86, 386–90.

    Article  CAS  PubMed  Google Scholar 

  53. Backs, J., & Olson, E. N. (2006). Control of cardiac growth by histone acetylation/deacetylation. Circulation Research, 98, 15–24.

    Article  CAS  PubMed  Google Scholar 

  54. Pasipoularides, A. (2012). Diastolic filling vortex forces and cardiac adaptations: probing the epigenetic nexus. Hellenic Journal of Cardiology, 53, 458–69.

    PubMed  Google Scholar 

  55. Pasipoularides, A. (2015). Linking genes to cardiovascular diseases: gene action and gene–environment interactions. Journal of Cardiovascular Translational Research, 8, 506–27.

    Article  PubMed  Google Scholar 

  56. Pasipoularides, A. (2013). Right and left ventricular diastolic pressure–volume relations: a comprehensive review. Journal of Cardiovascular Translational Research, 6, 239–52.

    Article  PubMed  Google Scholar 

  57. Pasipoularides, A., Palacios, I., Frist, W., Rosenthal, S., Newell, J. B., & Powell, W. J., Jr. (1985). Contribution of activation-inactivation dynamics to the impairment of relaxation in hypoxic cat papillary muscle. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 248, R54–62.

    CAS  Google Scholar 

  58. Pasipoularides, A., Mirsky, I., Hess, O. M., Grimm, J., & Krayenbuehl, H. P. (1986). Muscle relaxation and passive diastolic properties in man. Circulation, 74, 991–1001.

    Article  CAS  PubMed  Google Scholar 

  59. Mirsky, I., & Pasipoularides, A. (1990). Clinical assessment of diastolic function. Progress in Cardiovascular Diseases, 32, 291–318.

    Article  CAS  PubMed  Google Scholar 

  60. Mirsky, I., & Pasipoularides, A. (1980). Elastic properties of normal and hypertrophied cardiac muscle. Federation Proceeding, 39, 156–61.

    CAS  Google Scholar 

  61. Rader, F., Sachdev, E., Arsanjani, R., et al. (2015). Left ventricular hypertrophy in valvular aortic stenosis: mechanisms and clinical implications. American Journal of Medicine, 128, 344–52.

    Article  PubMed  Google Scholar 

  62. Cramariuc, D., Gerdts, E., Davidsen, E. S., Segadal, L., & Matre, K. (2010). Myocardial deformation in aortic valve stenosis: relation to left ventricular geometry. Heart, 96, 106–12.

    Article  PubMed  Google Scholar 

  63. Fielitz, J., Hein, S., Mitrovic, V., et al. (2001). Activation of the cardiac renin-angiotensin system and increased myocardial collagen expression in human aortic valve disease. Journal of the American College of Cardiology, 37, 1443–9.

    Article  CAS  PubMed  Google Scholar 

  64. Sebag, F. A., Lellouche, N., Chaachoui, N., et al. (2014). Prevalence and clinical impact of QRS duration in patients with lowflow/ low-gradient aortic stenosis due to left ventricular systolic dysfunction. European Journal of Heart Failure, 16, 639–47.

    Article  PubMed  Google Scholar 

  65. Wang, Y., & Hill, J. A. (2010). Electrophysiological remodeling in heart failure. Journal of Molecular and Cellular Cardiology, 48, 619–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Lipskaia, L., Chemaly, E. R., Hadri, L., Lompre, A., & Hajjar, R. J. (2010). Sarcoplasmic reticulum Ca2+ ATPase as a therapeutic target for heart failure. Expert Opinion on Biological Therapy, 10, 29–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Gelpi, R. J., Pasipoularides, A., Lader, A. S., et al. (1991). Changes in diastolic cardiac function in developing and stable perinephritic hypertension in conscious dogs. Circulation Research, 68, 555–67.

    Article  CAS  PubMed  Google Scholar 

  68. Vatner, S. F., Pagani, M., Manders, W. T., & Pasipoularides, A. (1980). Alpha adrenergic vasoconstriction and nitroglycerin vasodilation of large coronary arteries in the conscious dog. Journal of Clinical Investigation, 65, 5–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Vatner, S. F., Pasipoularides, A., & Mirsky, I. (1984). Measurement of arterial pressure-dimension relationships in conscious animals. Annals of Biomedical Engineering, 12, 521–34.

    Article  CAS  PubMed  Google Scholar 

  70. Marcus, M. L., Koyanagi, S., Harrison, D. G., Doty, D. B., Hiratzka, L. F., & Eastham, C. L. (1983). Abnormalities in the coronary circulation that occur as a consequence of cardiac hypertrophy. American Journal of Medicine, 75, 62–6.

    Article  CAS  PubMed  Google Scholar 

  71. Hittinger, L., Shannon, R. P., Bishop, S. P., Gelpi, R. J., & Vatner, S. F. (1989). Subendomyocardial exhaustion of blood flow reserve and increased fibrosis in conscious dogs with heart failure. Circulation Research, 65, 971–80.

    Article  CAS  PubMed  Google Scholar 

  72. Craig, W. E., Murgo, J. P., & Pasipoularides, A. (1987). Calculation of the time constant of relaxation. In W. Grossman & B. Lorell (Eds.), Diastolic relaxation of the heart (pp. 125–32). The Hague: Martinus Nijhoff.

    Chapter  Google Scholar 

  73. Pasipoularides, A. (2015). Fluid dynamics of ventricular filling in heart failure: overlooked problems of RV/LV chamber dilatation. Hellenic Journal of Cardiology, 56, 85–95.

    PubMed  PubMed Central  Google Scholar 

  74. Galiuto, L., Lotrionte, M., Crea, F., et al. (2006). Impaired coronary and myocardial flow in severe aortic stenosis is associated with increased apoptosis: a transthoracic Doppler and myocardial contrast echocardiography study. Heart, 92, 208–12.

    Article  CAS  PubMed  Google Scholar 

  75. Ihara, T., Shannon, R. P., Komamura, K., Pasipoularides, A., Patrick, T., Shen, Y. T., & Vatner, S. F. (1994). Effects of anaesthesia and recent surgery on diastolic function. Cardiovascular Research, 28, 325–36.

    Article  CAS  PubMed  Google Scholar 

  76. Martinou, J. C. (1999). Apoptosis: key to the mitochondrial gate. Nature, 399, 411–2.

    Article  CAS  PubMed  Google Scholar 

  77. Green, D. R. (2011). Means to an end: apoptosis and other cell death mechanisms. NY: Cold Spring Harbor, Cold Spring Harbor Laboratory Press.

    Google Scholar 

  78. Weber, K. T., Sun, Y., Bhattacharya, S. K., Ahokas, R. A., & Gerling, I. C. (2012). Myofibroblast-mediated mechanisms of pathological remodelling of the heart. Nature Reviews. Cardiology, 10, 15–26.

    Article  PubMed  CAS  Google Scholar 

  79. Huusko, J., Lottonen, L., Merentie, M., et al. (2012). AAV9-mediated VEGF-B gene transfer improves systolic function in progressive left ventricular hypertrophy. Molecular Therapy, 20, 2212–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Olson, E. N., & Schneider, M. D. (2003). Sizing up the heart: development redux in disease. Genes and Development, 17, 1937–56.

    Article  CAS  PubMed  Google Scholar 

  81. Huss, J. M., & Kelly, D. P. (2005). Mitochondrial energy metabolism in heart failure: a question of balance. Journal of Clinical Investigation, 115, 547–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Paulus, W. J., Grossman, W., Serizawa, T., Bourdillon, P. D., Pasipoularides, A., & Mirsky, I. (1985). Different effects of two types of ischemia on myocardial systolic and diastolic function. American Journal of Physiology. Heart and Circulatory Physiology, 248, H719–28.

    CAS  Google Scholar 

  83. Pasipoularides, A. (1988). On mechanisms of improved ejection fraction by early reperfusion in acute myocardial infarction: myocardial salvage or infarct stiffening? [Editorial]. Journal of the American College of Cardiology, 12, 1037–8.

    Article  CAS  PubMed  Google Scholar 

  84. Spinale, F. G. (2007). Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiological Reviews, 87, 1285–342.

    Article  CAS  PubMed  Google Scholar 

  85. Weber, K. T., Janicki, J. S., Shroff, S. G., Pick, R., Chen, R. M., & Bashey, R. I. (1988). Collagen remodeling of the pressure-overloaded, hypertrophied nonhuman primate myocardium. Circulation Research, 62, 757–65.

    Article  CAS  PubMed  Google Scholar 

  86. Kassiri, Z., & Khokha, R. (2005). Myocardial extra-cellular matrix and its regulation by metalloproteinases and their inhibitors. Thrombosis and Haemostasis, 93, 212–9.

    CAS  PubMed  Google Scholar 

  87. Chen, W., & Frangogiannis, N. G. (1833). Fibroblasts in post-infarction inflammation and cardiac repair. Biochimica et Biophysica Acta, 2013, 945–53.

    Google Scholar 

  88. Jugdutt, B. I. (2008). Aging and defective healing, adverse remodeling and blunted postconditioning in the wounded heart with aging. Journal of the American College of Cardiology, 51, 1399–403.

    Article  PubMed  Google Scholar 

  89. Biernacka, A., & Frangogiannis, N. G. (2011). Aging and cardiac fibrosis. Aging and Disease, 2, 158–73.

    PubMed  PubMed Central  Google Scholar 

  90. Grossman, W., Jones, D., & Mc Laurin, L. P. (1975). Wall stress and patterns of hypertrophy in the human left ventricle. Journal of Clinical Investigation, 56, 56–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Pasipoularides, A. (1990). Clinical assessment of ventricular ejection dynamics with and without outflow obstruction. Journal of the American College of Cardiology, 15, 859–82.

    Article  CAS  PubMed  Google Scholar 

  92. Pasipoularides, A., Murgo, J. P., Bird, J. J., & Craig, W. E. (1984). Fluid dynamics of aortic stenosis: mechanisms for the presence of subvalvular pressure gradients. American Journal of Physiology. Heart and Circulatory Physiology, 246, H542–H550.

    CAS  Google Scholar 

  93. Shim, Y., Hampton, T. G., Straley, C. A., Harrison, J. K., Spero, L. A., Bashore, T. M., & Pasipoularides, A. D. (1992). Ejection load changes in aortic stenosis: observations made following balloon aortic valvuloplasty. Circulation Research, 71, 1174–84.

    Article  CAS  PubMed  Google Scholar 

  94. Kupari, M., Laine, M., Turto, H., et al. (2013). Circulating collagen metabolites, myocardial fibrosis and heart failure in aortic valve stenosis. Journal of Heart Valve Disease, 22, 166–76.

    PubMed  Google Scholar 

  95. Pasipoularides, A. D., Shu, M., Shah, A., & Glower, D. D. (2002). Right ventricular diastolic relaxation in conscious dog models of pressure overload, volume overload and ischemia. Journal of Thoracic and Cardiovascular Surgery, 124, 964–72.

    Article  PubMed  Google Scholar 

  96. Pasipoularides, A. D., Shu, M., Shah, A., Silvestry, S., & Glower, D. D. (2002). Right ventricular diastolic function in canine models of pressure overload, volume overload and ischemia. American Journal of Physiology. Heart and Circulatory Physiology, 283, H2140–H2150.

    Article  CAS  PubMed  Google Scholar 

  97. Flett, A. S., Sado, D. M., Quarta, G., et al. (2012). Diffuse myocardial fibrosis in severe aortic stenosis: an equilibrium contrast cardiovascular magnetic resonance study. European Heart Journal Cardiovascular Imaging, 13, 819–26.

    Article  PubMed  Google Scholar 

  98. Sadoshima, J., & Izumo, S. (1997). The cellular and molecular response of cardiac myocytes to mechanical stress. Annual Review of Physiology, 59, 551–71.

    Article  CAS  PubMed  Google Scholar 

  99. Hill, J. A., & Olson, E. N. (2008). Cardiac plasticity. The New England Journal of Medicine, 358, 1370–80.

    Article  CAS  PubMed  Google Scholar 

  100. Chang, H. W., Kim, K. H., Kim, J. S., et al. (2013). Relationship between morphologic features of myocardial tissue and left ventricular function in patients with aortic valve disease and left ventricular hypertrophy. Journal of Heart Valve Disease, 22, 476–83.

    CAS  PubMed  Google Scholar 

  101. Levy, D., Garrison, R. J., Savage, D. D., Kannel, W. B., & Castelli, W. P. (1990). Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. The New England Journal of Medicine, 322, 1561–6.

    Article  CAS  PubMed  Google Scholar 

  102. Kupari, M., Turto, H., & Lommi, J. (2005). Left ventricular hypertrophy in aortic valve stenosis: preventive or promotive of systolic dysfunction and heart failure? European Heart Journal, 26, 1790–6.

    Article  PubMed  Google Scholar 

  103. Buermans, H. P. J., & Paulus, W. J. (2005). Iconoclasts topple adaptive myocardial hypertrophy in aortic stenosis. European Heart Journal, 26, 1697–9.

    Article  PubMed  Google Scholar 

  104. Hirt, M. N., Sörensen, N. A., Bartholdt, L. M., et al. (2012). Increased afterload induces pathological cardiac hypertrophy: a new in vitro model. Basic Research in Cardiology, 107, 1–16.

    Article  Google Scholar 

  105. Cioffi, G., Faggiano, P., Vizzardi, E., et al. (2011). Prognostic effect of inappropriately high left ventricular mass in asymptomatic severe aortic stenosis. Heart, 97, 301–7.

    Article  PubMed  Google Scholar 

  106. Hosseini, M. W. (2005). Molecular tectonics: from simple tectons to complex molecular networks. Accounts of Chemical Research, 38, 313–23.

    Article  CAS  PubMed  Google Scholar 

  107. Cooper, G., Kent, R. L., Uboh, C. E., Thompson, E. W., & Marino, T. A. (1985). Hemodynamic versus adrenergic control of cat right ventricular hypertrophy. Journal of Clinical Investigation, 75, 1403–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Kehat, I., & Molkentin, J. D. (2010). Molecular pathways underlying cardiac remodeling during pathophysiological stimulation. Circulation, 122, 2727–35.

    Article  PubMed  Google Scholar 

  109. Heyn, H., & Esteller, M. (2012). DNA methylation profiling in the clinic: applications and challenges. Nature Reviews. Genetics, 13, 679–92.

    Article  CAS  PubMed  Google Scholar 

  110. Kuwahara, K., Nishikimi, T., & Nakao, K. (2012). Transcriptional regulation of the fetal cardiac gene program. Journal of Pharmacological Sciences, 119, 198–203.

    Article  CAS  PubMed  Google Scholar 

  111. Ames, E. G., Lawson, M. J., Mackey, A. J., & Holmes, J. W. (2013). Sequencing of mRNA identifies re-expression of fetal splice variants in cardiac hypertrophy. Journal of Molecular and Cellular Cardiology, 62, 99–107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Hu, C. L., Chandra, R., Ge, H., et al. (2009). Adenylyl cyclase type 5 protein expression during cardiac development and stress. American Journal of Physiology. Heart and Circulatory Physiology, 297, H1776–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Vatner, S. F., Park, M., Yan, L., Lee, G. J., Lai, L., Iwatsubo, K., Ishikawa, Y., Pessin, J., & Vatner, D. E. (2013). Adenylyl cyclase type 5 in cardiac disease, metabolism, and aging. American Journal of Physiology. Heart and Circulatory Physiology, 305, H1–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Izumo, S., Nadal-Ginard, B., & Mahdavi, V. (1988). Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload. Proceedings of the National Academy of Sciences of the United States of America, 85, 339–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Pandya, K., Kim, H. S., & Smithies, O. (2006). Fibrosis, not cell size, delineates β-myosin heavy chain reexpression during cardiac hypertrophy and normal aging in vivo. Proceedings of the National Academy of Sciences of the United States of America, 103, 16864–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Lopez, J. E., Myagmar, B., Swigart, P. M., et al. (2011). β-Myosin heavy chain is induced by pressure overload in a minor subpopulation of smaller mouse cardiac myocytes. Circulation Research, 109, 629–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Pandya, K., & Smithies, O. (2011). β-MyHC and cardiac hypertrophy: size does matter. Circulation Research, 109, 609–10.

    Article  CAS  PubMed  Google Scholar 

  118. Isenberg, G., Kazanski, V., Kondratev, D., Gallitelli, M. F., Kiseleva, I., & Kamkin, A. (2003). Differential effects of stretch and compression on membrane currents and [Na+] c in ventricular myocytes. Progress in Biophysics and Molecular Biology, 82, 43–56.

    Article  CAS  PubMed  Google Scholar 

  119. Brancaccio, M., Fratta, L., Notte, A., et al. (2003). Melusin, a muscle-specific integrin β1-interacting protein, is required to prevent cardiac failure in response to chronic pressure overload. Nature Medicine, 9, 68–75.

    Article  CAS  PubMed  Google Scholar 

  120. Sugden, P. H., & Clerk, A. (1998). ‘Stress-responsive’ mitogen-activated protein kinases (c-Jun N-terminal kinases and p38 mitogen-activated protein kinases) in the myocardium. Circulation Research, 83, 345–52.

    Article  CAS  PubMed  Google Scholar 

  121. Duerr, R. L., Huang, S., Miraliakbar, H. R., Clark, R., Chien, K. R., & Ross, J., Jr. (1995). Insulin-like growth factor-1 enhances ventricular hypertrophy and function during the onset of experimental cardiac failure. Journal of Clinical Investigation, 95, 619–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Yamazaki, T., Komuro, I., Kudoh, S., et al. (1996). Endothelin-1 is involved in mechanical stress-induced cardiomyocyte hypertrophy. Journal of Biological Chemistry, 271, 3221–8.

    Article  CAS  PubMed  Google Scholar 

  123. Sheng, Z., Knowlton, K., Chen, J., Hoshijima, M., Brown, J. H., & Chien, K. R. (1997). Cardiotrophin 1 (CT-1) inhibition of cardiac myocyte apoptosis via a mitogen- activated protein kinase-dependent pathway: divergence from downstream CT-1 signals for myocardial cell hypertrophy. Journal of Biological Chemistry, 272, 5783–91.

    Article  CAS  PubMed  Google Scholar 

  124. Barnea, G., Strapps, W., Herrada, G., et al. (2008). The genetic design of signaling cascades to record receptor activation. Proceedings of the National Academy of Sciences of the United States of America, 105, 64–9.

    Article  CAS  PubMed  Google Scholar 

  125. van Berlo, J. H., Maillet, M., & Molkentin, J. D. (2013). Signaling effectors underlying pathologic growth and remodeling of the heart. Journal of Clinical Investigation, 123, 37–45.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  126. Adams, J. W., Sakata, Y., Davis, M. G., et al. (1998). Enhanced Gαq signaling: a common pathway mediates cardiac hypertrophy and apoptotic heart failure. Proceedings of the National Academy of Sciences of the United States of America, 95, 10140–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Sakata, Y., Hoit, B. D., Liggett, S. B., Walsh, R. A., & Dorn, G. W., II. (1998). Decompensation of pressure-overload hypertrophy in G alpha q-overexpressing mice. Circulation, 97, 1488–95.

    Article  CAS  PubMed  Google Scholar 

  128. Belmonte, S. L., & Blaxall, B. C. (2011). G protein coupled receptor kinases as therapeutic targets in cardiovascular disease. Circulation Research, 109, 309–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. DeWire, S. M., Ahn, S., Lefkowitz, R. J., & Shenoy, S. K. (2007). Beta-arrestins and cell signaling. Annual Review of Physiology, 69, 483–510.

    Article  CAS  PubMed  Google Scholar 

  130. Waters, C., Pyne, S., & Pyne, N. J. (2004). The role of G-protein coupled receptors and associated proteins in receptor tyrosine kinase signal transduction. Seminars in Cell and Developmental Biology, 15, 309–23.

    Article  CAS  PubMed  Google Scholar 

  131. van Biesen, T., Hawes, B. E., Luttrell, D. K., et al. (1995). Receptor-tyrosine-kinase- and G beta gamma-mediated MAP kinase activation by a common signalling pathway. Nature, 376, 781–4.

    Article  PubMed  Google Scholar 

  132. Luttrell, L. M., Daaka, Y., & Lefkowitz, R. J. (1999). Regulation of tyrosine kinase cascades by G-protein-coupled receptors. Current Opinion in Cell Biology, 11, 177–83.

    Article  CAS  PubMed  Google Scholar 

  133. Rockman, H. A., Koch, W. J., & Lefkowitz, R. J. (2002). Seven-transmembrane-spanning receptors and heart function. Nature, 415, 206–12.

    Article  CAS  PubMed  Google Scholar 

  134. Noor, N., Patel, C. B., & Rockman, H. A. (2011). Beta-arrestin: a signaling molecule and potential therapeutic target for heart failure. Journal of Molecular and Cellular Cardiology, 51, 534–41.

    Article  CAS  PubMed  Google Scholar 

  135. Port, J. D., & Bristow, M. R. (2001). Altered beta-adrenergic receptor gene regulation and signaling in chronic heart failure. Journal of Molecular and Cellular Cardiology, 33, 887–905.

    Article  CAS  PubMed  Google Scholar 

  136. Packer, M., Bristow, M. R., Cohn, J. N., et al. (1996). The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. The New England Journal of Medicine, 334, 1349–55.

    Article  CAS  PubMed  Google Scholar 

  137. Cohn, J. N., & Tognoni, G. (2001). Valsartan Heart Failure Trial I. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. The New England Journal of Medicine, 345, 1667–75.

    Article  CAS  PubMed  Google Scholar 

  138. Paul, M., Poyan Mehr, A., & Kreutz, R. (2006). Physiology of local renin-angiotensin systems. Physiological Reviews, 86, 747–803.

    Article  CAS  PubMed  Google Scholar 

  139. Li, Y., Li, X. H., & Yuan, H. (2012). Angiotensin II type-2 receptor-specific effects on the cardiovascular system. Cardiovascular Diagnostic and Therapy, 2, 56–62.

    Google Scholar 

  140. Reiter, E., Ahn, S., Shukla, A. K., & Lefkowitz, R. J. (2012). Molecular mechanism of β-arrestin-biased agonism at seven-transmembrane receptors. Annual Review of Pharmacology and Toxicology, 52, 179–97.

    Article  CAS  PubMed  Google Scholar 

  141. Bylund, D. B., Eikenberg, D. C., Hieble, J. P., et al. (1994). International Union of Pharmacology nomenclature of adrenoceptors. Pharmacological Reviews, 46, 121–36.

    CAS  PubMed  Google Scholar 

  142. Triposkiadis, F., Karayannis, G., Giamouzis, G., et al. (2009). The sympathetic nervous system in heart failure. Journal of the American College of Cardiology, 54, 1747–62.

    Article  CAS  PubMed  Google Scholar 

  143. Feldman, D. S., Carnes, C. A., Abraham, W. T., & Bristow, M. R. (2005). Mechanisms of disease: beta-adrenergic receptors—alterations in signal transduction and pharmacogenomics in heart failure. Nature Clinical Practice. Cardiovascular Medicine, 2, 475–83.

    Article  CAS  PubMed  Google Scholar 

  144. Molkentin, J. D., & Dorn, G. W., II. (2001). Cytoplasmic signaling pathways that regulate cardiac hypertrophy. Annual Review of Physiology, 63, 391–426.

    Article  CAS  PubMed  Google Scholar 

  145. Charron, F., Paradis, P., Bronchain, O., Nemer, G., & Nemer, M. (1999). Cooperative interaction between GATA-4 and GATA-6 regulates myocardial gene expression. Molecular and Cellular Biology, 19, 4355–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Zhou, P., He, A., & Pu, W. T. (2012). Regulation of GATA4 transcriptional activity in cardiovascular development and disease. Current Topics in Developmental Biology, 100, 143–69.

    Article  CAS  PubMed  Google Scholar 

  147. Peterkin, T., Gibson, A., Loose, M., & Patient, R. (2005). The roles of GATA-4, -5 and -6 in vertebrate heart development. Seminars in Cell and Developmental Biology, 16, 83–94.

    Article  CAS  PubMed  Google Scholar 

  148. Pikkarainen, S., Tokola, H., Kerkela, R., & Ruskoaho, H. (2004). GATA transcription factors in the developing and adult heart. Cardiovascular Research, 63, 196–207.

    Article  CAS  PubMed  Google Scholar 

  149. Liang, Q., & Molkentin, J. D. (2002). Divergent signaling pathways converge on GATA4 to regulate cardiac hypertrophic gene expression. Journal of Molecular and Cellular Cardiology, 34, 611–6.

    Article  CAS  PubMed  Google Scholar 

  150. van Berlo, J. H., Elrod, J. W., van den Hoogenhof, M. M., et al. (2010). The transcription factor GATA-6 regulates pathological cardiac hypertrophy. Circulation Research, 107, 1032–40.

    Article  PubMed  CAS  Google Scholar 

  151. Akazawa, H., & Komuro, I. (2003). Roles of cardiac transcription factors in cardiac hypertrophy. Circulation Research, 92, 1079–88.

    Article  CAS  PubMed  Google Scholar 

  152. Oka, T., Maillet, M., Watt, A. J., Schwartz, R. J., Aronow, B. J., Duncan, S. A., & Molkentin, J. D. (2006). Cardiac-specific deletion of Gata4 reveals its requirement for hypertrophy, compensation, and myocyte viability. Circulation Research, 98, 837–45.

    Article  CAS  PubMed  Google Scholar 

  153. Oka, T., Xu, J., & Molkentin, J. D. (2007). Re-employment of developmental transcription factors in adult heart disease. Seminars in Cell and Developmental Biology, 18, 117–31.

    Article  CAS  PubMed  Google Scholar 

  154. Papait, R., Kunderfranco, P., Stirparo, G. G., Latronico, M. V., & Condorelli, G. (2013). Long noncoding RNA: a new player of heart failure? Journal of Cardiovascular Translational Research, 6, 876–83.

    Article  PubMed  PubMed Central  Google Scholar 

  155. Peters, T., & Schroen, B. (2014). Missing links in cardiology: long non-coding RNAs enter the arena. Pflügers Archiv, 466, 1177–87.

    Article  CAS  PubMed  Google Scholar 

  156. Barbato, E., Lara-Pezzi, E., Stolen, C., Taylor, A., Barton, P. J., Bartunek, J., Iaizzo, P., Judge, D. P., Kirshenbaum, L., Blaxall, B. C., Terzic, A., & Hall, J. L. (2014). Advances in induced pluripotent stem cells, genomics, biomarkers, and antiplatelet therapy highlights of the year in JCTR 2013. Journal of Cardiovascular Translational Research, 7, 518–25.

    Article  PubMed  PubMed Central  Google Scholar 

  157. Chen, L., Qin, F., Ge, M., Shu, Q., & Xu, J. (2014). Application of adipose-derived stem cells in heart disease. Journal of Cardiovascular Translational Research, 7, 651–63.

    Article  PubMed  Google Scholar 

  158. Bernal, J. A. (2013). RNA-based tools for nuclear reprogramming and lineage-conversion: towards clinical applications. Journal of Cardiovascular Translational Research, 6, 956–68.

    Article  PubMed  PubMed Central  Google Scholar 

  159. Inagawa, K., & Ieda, M. (2013). Direct reprogramming of mouse fibroblasts into cardiac myocytes. Journal of Cardiovascular Translational Research, 6, 37–45.

    Article  PubMed  Google Scholar 

  160. Hudson, J. E., & Porrello, E. R. (2013). The non-coding road towards cardiac regeneration. Journal of Cardiovascular Translational Research, 6, 909–23.

    Article  PubMed  Google Scholar 

  161. Wang, K., Liu, F., Zhou, L. Y., et al. (2014). The long noncoding RNA CHRF regulates cardiac hypertrophy by targeting miR-489. Circulation Research, 114, 1377–88.

    Article  CAS  PubMed  Google Scholar 

  162. Bartel, D. P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116, 281–97.

    Article  CAS  PubMed  Google Scholar 

  163. Lim, L. P., Lau, N. C., Garrett-Engele, P., et al. (2005). Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature, 433, 769–73.

    Article  CAS  PubMed  Google Scholar 

  164. Ambros, V. (2004). The functions of animal microRNAs. Nature, 431, 350–5.

    Article  CAS  PubMed  Google Scholar 

  165. Lee, R. C., Feinbaum, R. L., & Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 75, 843–54.

    Article  CAS  PubMed  Google Scholar 

  166. Sevignani, C., Calin, G. A., Siracusa, L. D., & Croce, C. M. (2006). Mammalian microRNAs: a small world for fine-tuning gene expression. Mammalian Genome, 17, 189–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. van Rooij, E., Sutherland, L. B., Qi, X., Richardson, J. A., Hill, J., & Olson, E. N. (2007). Control of stress-dependent cardiac growth and gene expression by a microRNA. Science, 316, 575–9.

    Article  PubMed  CAS  Google Scholar 

  168. Catalucci, D., Gallo, P., & Condorelli, G. (2009). MicroRNAs in cardiovascular biology and heart disease. Circulation. Cardiovascular Genetics, 2, 402–8.

    Article  CAS  PubMed  Google Scholar 

  169. Latronico, M. V. G., Condorelli, G., & Dorn, G. W., II. (2010). MicroRNAs in heart disease: putative novel therapeutic targets? European Heart Journal, 31, 649–58.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  170. Dorn, G. W., II. (2011). MicroRNAs in cardiac disease. Translational Research, 157, 226–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Papoutsidakis, N., Deftereos, S., Kaoukis, A., et al. (2013). MicroRNAs and the heart: small things do matter. Current Topics in Medicinal Chemistry, 13, 216–30.

    Article  CAS  PubMed  Google Scholar 

  172. Polacek, D. C., Passerini, A. G., Shi, C., et al. (2003). Fidelity and enhanced sensitivity of differential transcription profiles following linear amplification of nanogram amounts of endothelial mRNA. Physiological Genomics, 13, 147–156.

    Article  CAS  PubMed  Google Scholar 

  173. Puskás, L. G., Zvara, A., Hackler, L., Jr., & Van Hummelen, P. (2002). RNA amplification results in reproducible microarray data with slight ratio bias. BioTechniques, 32, 1330–40.

    PubMed  Google Scholar 

  174. Yu, L. M., & Xu, Y. (2015). Epigenetic regulation in cardiac fibrosis. World Journal Cardiology, 7, 784–91.

    Article  Google Scholar 

  175. Villar, A. V., Garcia, R., Merino, D., et al. (2013). Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients. International Journal of Cardiology, 167, 2875–81.

    Article  PubMed  Google Scholar 

  176. Haghikia, A., & Hilfiker-Kleiner, D. (2009). MiRNA-21: a key to controlling the cardiac fibroblast compartment? Cardiovascular Research, 82, 1–3.

    Article  CAS  PubMed  Google Scholar 

  177. Cheng, Y., Ji, R., Yue, J., et al. (2007). MicroRNAs are aberrantly expressed in hypertrophic heart: do they play a role in cardiac hypertrophy? American Journal of Pathology, 170, 1831–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Chen, Z., Li, C., Xu, Y., et al. (2014). Circulating level of miR-378 predicts left ventricular hypertrophy in patients with aortic stenosis. PLoS One, 9(8), e105702.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  179. Carè, A., Catalucci, D., Felicetti, F., et al. (2007). MicroRNA-133 controls cardiac hypertrophy. Nature Medicine, 13, 613–8.

    Article  PubMed  CAS  Google Scholar 

  180. Araque, J. C., Greason, K. L., Suri, R. M., et al. (2016). The role of balloon aortic valvuloplasty in patients with aortic valve stenosis and society of thoracic surgeons risk of 15% or higher. Annals of Thoracic Surgery, 101, 592–8.

    Article  PubMed  Google Scholar 

  181. Khawaja, M. Z., Sohal, M., Valli, H., et al. (2013). Standalone balloon aortic valvuloplasty: indications and outcomes from the UK in the transcatheter valve era. Catheterization and Cardiovascular Interventions, 81, 366–73.

    Article  PubMed  Google Scholar 

  182. Nishimura, R. A., Otto, C. M., Bonow, R. O., et al. (2014). AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology, 63, 2438–88.

    Article  PubMed  Google Scholar 

  183. Cribier, A., Eltchaninoff, H., & Tron, C. (2006). Percutaneous implantation of aortic valve prosthesis in patients with calcific aortic stenosis: technical advances, clinical results and future strategies. Journal of Interventional Cardiology, 19, S87–S96.

    Article  Google Scholar 

  184. Clavel, M. A., Webb, J. G., Rodés-Cabau, J., et al. (2010). Comparison between transcatheter and surgical prosthetic valve implantation in patients with severe aortic stenosis and reduced left ventricular ejection fraction. Circulation, 122, 1928–36.

    Article  CAS  PubMed  Google Scholar 

  185. Smith, C. R., Leon, M. B., Mack, M. J., et al. (2011). Transcatheter versus surgical aortic-valve replacement in high-risk patients. The New England Journal of Medicine, 364, 2187–98.

    Article  CAS  PubMed  Google Scholar 

  186. Vizzardi, E., D'Aloia, A., Fiorina, C., et al. (2012). Early regression of left ventricular mass associated with diastolic improvement after transcatheter aortic valve implantation. Journal of the American Society of Echocardiography, 25, 1091–8.

    Article  PubMed  Google Scholar 

  187. Nagaraja, V., Raval, J., Eslick, G. D., & Ong, A. T. (2014). Transcatheter versus surgical aortic valve replacement: a systematic review and meta-analysis of randomised and non-randomised trials. Open Heart, 1, e000013.

    Article  PubMed  PubMed Central  Google Scholar 

  188. Taniguchi, T., Morimoto, T., Shiomi, H., et al. (2015). Initial surgical versus conservative strategies in patients with asymptomatic severe aortic stenosis. Journal of the American College of Cardiology. doi:10.1016/j.jacc.2015.10.001.

    PubMed  Google Scholar 

  189. Leon, M. B., Smith, C. R., Mack, M., et al. (2010). Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. The New England Journal of Medicine, 363, 1597–607.

    Article  CAS  PubMed  Google Scholar 

  190. Beach, J. M., Mihaljevic, T., Rajeswaran, J., et al. (2014). Ventricular hypertrophy and left atrial dilatation persist and are associated with reduced survival after valve replacement for aortic stenosis. Journal of Thoracic and Cardiovascular Surgery, 147, 362–9.

    Article  PubMed  Google Scholar 

  191. Friddle, C. J., Koga, T., Rubin, E. M., & Bristow, J. (2000). Expression profiling reveals distinct sets of genes altered during induction and regression of cardiac hypertrophy. Proceedings of the National Academy of Sciences of the United States of America, 97, 6745–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Stansfield, W. E., Charles, P. C., Tang, R. H., et al. (2009). Regression of pressure-induced left ventricular hypertrophy is characterized by a distinct gene expression profile. Journal of Thoracic and Cardiovascular Surgery, 137, 232–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Bjornstad, J. L., Skrbic, B., Sjaastad, I., et al. (2012). A mouse model of reverse cardiac remodelling following banding-debanding of the ascending aorta. Acta Physiologica, 205, 92–102.

    Article  CAS  PubMed  Google Scholar 

  194. Pasipoularides, A., Murgo, J. P., Miller, J. W., & Craig, W. E. (1987). Nonobstructive left ventricular ejection pressure gradients in man. Circulation Research, 61, 220–7.

    Article  CAS  PubMed  Google Scholar 

  195. Sharma, U. C., Barenbrug, P., Pokharel, S., Dassen, W. R., Pinto, Y. M., & Maessen, J. G. (2004). Systematic review of the outcome of aortic valve replacement in patients with aortic stenosis. Annals of Thoracic Surgery, 78, 90–5.

    Article  PubMed  Google Scholar 

  196. Bauer, F., Coutant, V., Bernard, M., et al. (2013). Patients with severe aortic stenosis and reduced ejection fraction: earlier recovery of left ventricular systolic function after transcatheter aortic valve implantation compared with surgical valve replacement. Echocardiography, 30, 865–70.

    Article  PubMed  Google Scholar 

  197. Adams, D. H., Popma, J. J., Reardon, M. J., et al. (2014). Transcatheter aortic-valve replacement with a self-expanding prosthesis. The New England Journal of Medicine, 370, 1790–8.

    Article  CAS  PubMed  Google Scholar 

  198. Reardon, M. J., Adams, D. H., Kleiman, N. S., et al. (2015). 2-year outcomes in patients undergoing surgical or self-expanding transcatheter aortic valve replacement. Journal of the American College of Cardiology, 66, 113–21.

    Article  PubMed  Google Scholar 

  199. Kim, S. J., Samad, Z., Bloomfield, G. S., & Douglas, P. S. (2014). A critical review of hemodynamic changes and left ventricular remodeling after surgical aortic valve replacement and percutaneous aortic valve replacement. American Heart Journal, 168, 150–9.

    Article  PubMed  Google Scholar 

  200. Hahn, R. T., Pibarot, P., Stewart, W. J., et al. (2013). Comparison of transcatheter and surgical aortic valve replacement in severe aortic stenosis: a longitudinal study of echocardiography parameters in cohort A of the PARTNER trial (placement of aortic transcatheter valves). Journal of the American College of Cardiology, 61, 2514–21.

    Article  PubMed  PubMed Central  Google Scholar 

  201. Zajarias, A., & Cribier, A. G. (2009). Outcomes and safety of percutaneous aortic valve replacement. Journal of the American College of Cardiology, 53, 1829–36.

    Article  PubMed  Google Scholar 

  202. Milano, A. D., Faggian, G., Dodonov, M., et al. (2012). Prognostic value of myocardial fibrosis in patients with severe aortic valve stenosis. Journal of Thoracic and Cardiovascular Surgery, 144, 830–7.

    Article  PubMed  Google Scholar 

  203. Regitz-Zagrosek, V., Brokat, S., & Tschope, C. (2007). Role of gender in heart failure with normal left ventricular ejection fraction. Progress in Cardiovascular Diseases, 49, 241–51.

    Article  CAS  PubMed  Google Scholar 

  204. Devereux, R. B., Roman, M. J., Liu, J. E., et al. (2000). Congestive heart failure despite normal left ventricular systolic function in a population-based sample: the strong heart study. American Journal of Cardiology, 86, 1090–6.

    Article  CAS  PubMed  Google Scholar 

  205. Carroll, J. D., Carroll, E. P., Feldman, T., et al. (1992). Sex associated differences in left ventricular function in aortic stenosis of the elderly. Circulation, 86, 1099–107.

    Article  CAS  PubMed  Google Scholar 

  206. Aurigemma, G. P., Silver, K. H., McLaughlin, M., Mauser, J., & Gaasch, W. H. (1994). Impact of chamber geometry and gender on left ventricular systolic function in patients > 60 years of age with aortic stenosis. American Journal of Cardiology, 74, 794–8.

    Article  CAS  PubMed  Google Scholar 

  207. Aurigemma, G. P., & Gaasch, W. H. (1995). Gender differences in older patients with pressure-overload hypertrophy of the left ventricle. Cardiology, 86, 310–7.

    Article  CAS  PubMed  Google Scholar 

  208. Douglas, P. S., Katz, S. E., Weinberg, E. O., Chen, M. H., Bishop, S. P., & Lorell, B. H. (1998). Hypertrophic remodeling: gender differences in the early response to left ventricular pressure overload. Journal of the American College of Cardiology, 32, 1118–25.

    Article  CAS  PubMed  Google Scholar 

  209. Douglas, P. S., Otto, C. M., Mickel, M. C., Labovitz, A., Reid, C. L., & Davis, K. B. (1995). Gender differences in left ventricle geometry and function in patients undergoing balloon dilatation of the aortic valve for isolated aortic stenosis. NHLBI Balloon Valvuloplasty Registry. British Heart Journal, 73, 548–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Villari, B., Campbell, S. E., Schneider, J., Vassalli, G., Chiariello, M., & Hess, O. M. (1995). Sex-dependent differences in left ventricular function and structure in chronic pressure overload. European Heart Journal, 16, 1410–9.

    CAS  PubMed  Google Scholar 

  211. Regitz-Zagrosek, V. (2006). Therapeutic implications of the gender-specific aspects of cardiovascular disease. Nature Reviews. Drug Discovery, 5, 425–38.

    Article  CAS  PubMed  Google Scholar 

  212. Petrov, G., Dworatzek, E., Schulze, T. M., et al. (2014). Maladaptive remodeling is associated with impaired survival in women but not in men after aortic valve replacement. Journal of the American College of Cardiology: Cardiovascular Imaging, 7, 1073–80.

    Article  Google Scholar 

  213. Dworatzek, E., Mahmoodzadeh, S., Schubert, C., et al. (2014). Sex differences in exercise-induced physiological myocardial hypertrophy are modulated by oestrogen receptor beta. Cardiovascular Research, 102, 418–28.

    Article  CAS  PubMed  Google Scholar 

  214. Kuiper, G. G., Enmark, E., Pelto-Huikko, M., Nilsson, S., & Gustafsson, J. A. (1996). Cloning of a novel receptor expressed in rat prostate and ovary. Proceedings of the National Academy of Sciences of the United States of America, 93, 5925–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Mosselman, S., Polman, J., & Dijkema, R. (1996). ER beta: identification and characterization of a novel human estrogen receptor. FEBS Letters, 392, 49–53.

    Article  CAS  PubMed  Google Scholar 

  216. Levy, D., Larson, M. G., Vasan, R. S., Kannel, W. B., & Ho, K. K. (1996). The progression from hypertension to congestive heart failure. JAMA, 275, 1557–62.

    Article  CAS  PubMed  Google Scholar 

  217. Petrov, G., Regitz-Zagrosek, V., Lehmkuhl, E., et al. (2010). Regression of myocardial hypertrophy after aortic valve replacement: faster in women? Circulation, 122, S23–S28.

    Article  PubMed  Google Scholar 

  218. Alberts, I. L., Wess, T. J., Cameron, G. J., & Laing, J. H. (2002). Structure of type I and type III heterotypic collagen fibrils: an x-ray diffraction study. Journal of Structural Biology, 137, 15–22.

    Article  PubMed  CAS  Google Scholar 

  219. Turner, N. A., & Porter, K. E. (2012). Regulation of myocardial matrix metalloproteinase expression and activity by cardiac fibroblasts. Life, 64(2), 143–50.

    CAS  PubMed  Google Scholar 

  220. Fliegner, D., Schubert, C., Penkalla, A., et al. (2010). Female sex and estrogen receptor-b attenuate cardiac remodeling and apoptosis in pressure overload. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 298, 1597–1606.

    Article  CAS  Google Scholar 

  221. Legget, M. E., Kuusisto, J., Healy, N. L., Fujioka, M., Schwaegler, R. G., & Otto, C. M. (1996). Gender differences in left ventricular function at rest and with exercise in asymptomatic aortic stenosis. American Heart Journal, 131, 94–100.

    Article  CAS  PubMed  Google Scholar 

  222. Fielitz, J., Leuschner, M., Zurbrugg, H. R., et al. (2004). Regulation of matrix metalloproteinases and their inhibitors in the left ventricular myocardium of patients with aortic stenosis. Journal of Molecular Medicine, 12, 809–20.

    Article  CAS  Google Scholar 

  223. Mahmoodzadeh, S., Dworatzek, E., Fritschka, S., Pham, T. H., & Regitz-Zagrosek, V. (2010). 17beta-Estradiol inhibits matrix metalloproteinase-2 transcription via MAP kinase in fibroblasts. Cardiovascular Research, 85, 719–28.

    Article  CAS  PubMed  Google Scholar 

  224. Fliegner, D., Schubert, C., Penkalla, A., et al. (2010). Female sex and estrogen receptor-β attenuate cardiac remodeling and apoptosis in pressure overload. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 298, R1597–606.

    Article  CAS  PubMed  Google Scholar 

  225. Hayashida, K., Morice, M. C., Chevalier, B., et al. (2012). Sex-related differences in clinical presentation and outcome of transcatheter aortic valve implantation for severe aortic stenosis. Journal of the American College of Cardiology, 59, 566–71.

    Article  PubMed  Google Scholar 

  226. Hamed, O., Persson, P. J., Engel, A. M., McDonough, S., & Smith, J. M. (2009). Gender differences in outcomes following aortic valve replacement surgery. International Journal of Surgery, 7, 214–7.

    Article  PubMed  Google Scholar 

  227. Stangl, V., Baldenhofer, G., Knebel, F., et al. (2012). Impact of gender on three-month outcome and left ventricular remodeling after transfemoral transcatheter aortic valve implantation. American Journal of Cardiology, 110, 884–90.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Duke University School of Medicine, Durham, NC, USA

    Ares Pasipoularides

  2. Duke/NSF Research Center for Emerging Cardiovascular Technologies, Duke University, Durham, NC, 27710, USA

    Ares Pasipoularides

Authors
  1. Ares Pasipoularides
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ares Pasipoularides.

Ethics declarations

Fully compliant

Sources of Funding

Research support, for work from my laboratory surveyed here, was provided by National Heart, Lung, and Blood Institute, Grant R01 HL 050446; National Science Foundation, Grant CDR 8622201; and North Carolina Supercomputing Center and Cray Research.

Conflict of interest

I declare that I have no conflict of interest, whatsoever.

Ethical Approval

All procedures performed in studies involving human participants that are reviewed here were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments. All applicable international, national, and/or institutional guidelines for the care and use of animals in studies involving animals that are reviewed here were followed.

Additional information

Associate Editor Jennifer L. Hall oversaw the review of this article

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pasipoularides, A. Calcific Aortic Valve Disease: Part 2—Morphomechanical Abnormalities, Gene Reexpression, and Gender Effects on Ventricular Hypertrophy and Its Reversibility. J. of Cardiovasc. Trans. Res. 9, 374–399 (2016). https://doi.org/10.1007/s12265-016-9695-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-016-9695-z

Keywords

Search

Navigation