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Advances in Heart Valve Biomechanics pp 241–262Cite as

Mechanical Mediation of Signaling Pathways in Heart Valve Development and Disease

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Abstract

Heart valves are elegant, dynamic, pliable structures experiencing complex and varied mechanical forces during development and throughout the course of their postnatal lifetime. Recent work has shown a remarkable link between the mechanical environment of these valve leaflets and their structure, function, and biological behavior. Additionally, these mechanobiological responses, while being regulated by a similar set of signaling pathways, may be very different depending on their occurrence during valvulogenesis or during adulthood. This chapter reviews what is currently known about these differentially mechanoregulated signaling pathways in the heart valve, highlighting any gaps in knowledge.

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References

  1. Balachandran K, Sucosky P, Yoganathan AP. Hemodynamics and mechanobiology of aortic valve inflammation and calcification. Int J Inflam. 2011;2011:263870.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Sacks MS, David Merryman W, Schmidt DE. On the biomechanics of heart valve function. J Biomech. 2009;42(12):1804–24.

    PubMed  PubMed Central  Google Scholar 

  3. Sacks MS, Yoganathan AP. Heart valve function: a biomechanical perspective. Philos Trans R Soc Lond B Biol Sci. 2007;362(1484):1369–91.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Merryman WD, et al. Synergistic effects of cyclic tension and transforming growth factor-beta1 on the aortic valve myofibroblast. Cardiovasc Pathol. 2007;16(5):268–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Merryman WD, et al. Differences in tissue-remodeling potential of aortic and pulmonary heart valve interstitial cells. Tissue Eng. 2007;13:2281.

    Article  PubMed  Google Scholar 

  6. Huang HY, Liao J, Sacks MS. In-situ deformation of the aortic valve interstitial cell nucleus under diastolic loading. J Biomech Eng. 2007;129(6):880–9.

    Article  PubMed  Google Scholar 

  7. Balachandran K, et al. Elevated cyclic stretch induces aortic valve calcification in a bone morphogenic protein-dependent manner. Am J Pathol. 2010;177(1):49–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Butcher JT, Nerem RM. Valvular endothelial cells regulate the phenotype of interstitial cells in co-culture: effects of steady shear stress. Tissue Eng. 2006;12(4):905–15.

    Article  CAS  PubMed  Google Scholar 

  9. Mahler GJ, Butcher JT. Inflammatory regulation of valvular remodeling: the good(?), the bad, and the ugly. Int J Inflam. 2011;2011:721419.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Atkins SK, et al. Bicuspid aortic valve hemodynamics induces abnormal medial remodeling in the convexity of porcine ascending aortas. Biomech Model Mechanobiol. 2014;13:1209.

    Article  PubMed  Google Scholar 

  11. Richards JM, et al. The mechanobiology of mitral valve function, degeneration, and repair. J Vet Cardiol. 2012;14(1):47–58.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Balachandran K, et al. Cyclic strain induces dual-mode endothelial-mesenchymal transformation of the cardiac valve. Proc Natl Acad Sci U S A. 2011;108(50):19943–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Markwald RR, Butcher JT. The next frontier in cardiovascular developmental biology—an integrated approach to adult disease? Nat Clin Pract Cardiovasc Med. 2007;4(2):60–1.

    Article  PubMed  Google Scholar 

  14. Wylie-Sears J, et al. Mitral valve endothelial cells with osteogenic differentiation potential. Arterioscler Thromb Vasc Biol. 2011;31(3):598–607.

    Article  CAS  PubMed  Google Scholar 

  15. Goodwin RL, et al. Three-dimensional model system of valvulogenesis. Dev Dyn. 2005;233(1):122–9.

    Article  PubMed  Google Scholar 

  16. Lindsey SE, Butcher JT, Yalcin HC. Mechanical regulation of cardiac development. Front Physiol. 2014;5:318.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Butcher JT, Simmons CA, Warnock JN. Mechanobiology of the aortic heart valve. J Heart Valve Dis. 2008;17(1):62–73.

    PubMed  Google Scholar 

  18. Armstrong EJ, Bischoff J. Heart valve development: endothelial cell signaling and differentiation. Circ Res. 2004;95(5):459–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Combs MD, Yutzey KE. VEGF and RANKL regulation of NFATc1 in heart valve development. Circ Res. 2009;105(6):565–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Combs MD, Yutzey KE. Heart valve development: regulatory networks in development and disease. Circ Res. 2009;105(5):408–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhou J, et al. Cadherin-11 expression patterns in heart valves associate with key functions during embryonic cushion formation, valve maturation and calcification. Cells Tissues Organs. 2013;198(4):300–10.

    Article  CAS  PubMed  Google Scholar 

  22. Moskowitz IP, et al. Transcription factor genes Smad4 and Gata4 cooperatively regulate cardiac valve development. Proc Natl Acad Sci U S A. 2011;108(10):4006–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hinton RB, Yutzey KE. Heart valve structure and function in development and disease. Annu Rev Physiol. 2011;73:29–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lindsey SE, Butcher JT. The cycle of form and function in cardiac valvulogenesis. Aswan Heart Cent Sci Pract Ser. 2011;2011:10.

    Article  Google Scholar 

  25. Goenezen S, Rennie MY, Rugonyi S. Biomechanics of early cardiac development. Biomech Model Mechanobiol. 2012;11(8):1187–204.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Granados-Riveron JT, Brook JD. The impact of mechanical forces in heart morphogenesis. Circ Cardiovasc Genet. 2012;5(1):132–42.

    Article  CAS  PubMed  Google Scholar 

  27. Boselli F, Freund JB, Vermot J. Blood flow mechanics in cardiovascular development. Cell Mol Life Sci. 2015;72(13):2545–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Steed E, Boselli F, Vermot J. Hemodynamics driven cardiac valve morphogenesis. Biochim Biophys Acta. 2016;1863(7B):1760–6.

    Article  CAS  PubMed  Google Scholar 

  29. Johnson B, et al. Altered mechanical state in the embryonic heart results in time-dependent decreases in cardiac function. Biomech Model Mechanobiol. 2015;14(6):1379–89.

    Article  PubMed  Google Scholar 

  30. Kalogirou S, et al. Intracardiac flow dynamics regulate atrioventricular valve morphogenesis. Cardiovasc Res. 2014;104(1):49–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Tao G, Kotick JD, Lincoln J. Heart valve development, maintenance, and disease: the role of endothelial cells. Curr Top Dev Biol. 2012;100:203–32.

    Article  CAS  PubMed  Google Scholar 

  32. Chester AH, et al. The living aortic valve: from molecules to function. Global Cardiol Sci Pract. 2014;2014(1):52–77.

    Google Scholar 

  33. Back M, et al. Biomechanical factors in the biology of aortic wall and aortic valve diseases. Cardiovasc Res. 2013;99(2):232–41.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Riem Vis PW, et al. Environmental regulation of valvulogenesis: implications for tissue engineering. Eur J Cardiothorac Surg. 2011;39(1):8–17.

    Article  PubMed  Google Scholar 

  35. Camenisch TD, et al. Heart-valve mesenchyme formation is dependent on hyaluronan-augmented activation of ErbB2-ErbB3 receptors. Nat Med. 2002;8(8):850–5.

    Article  CAS  PubMed  Google Scholar 

  36. Miquerol L, Langille BL, Nagy A. Embryonic development is disrupted by modest increases in vascular endothelial growth factor gene expression. Development. 2000;127(18):3941–6.

    CAS  PubMed  Google Scholar 

  37. Hallaq H, et al. A null mutation of Hhex results in abnormal cardiac development, defective vasculogenesis and elevated Vegfa levels. Development. 2004;131(20):5197–209.

    Article  CAS  PubMed  Google Scholar 

  38. Butcher JT, Markwald RR. Valvulogenesis: the moving target. Philos Trans R Soc Lond B Biol Sci. 2007;362(1484):1489–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Johnson EN, et al. NFATc1 mediates vascular endothelial growth factor-induced proliferation of human pulmonary valve endothelial cells. J Biol Chem. 2003;278(3):1686–92.

    Article  CAS  PubMed  Google Scholar 

  40. Rabkin E, et al. Activated interstitial myofibroblasts express catabolic enzymes and mediate matrix remodeling in myxomatous heart valves. Circulation. 2001;104(21):2525–32.

    Article  CAS  PubMed  Google Scholar 

  41. Chang CP, et al. A field of myocardial-endocardial NFAT signaling underlies heart valve morphogenesis. Cell. 2004;118(5):649–63.

    Article  CAS  PubMed  Google Scholar 

  42. de la Pompa JL, et al. Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and septum. Nature. 1998;392(6672):182–6.

    Article  CAS  PubMed  Google Scholar 

  43. Lambrechts D, Carmeliet P. Sculpting heart valves with NFATc and VEGF. Cell. 2004;118(5):532–4.

    Article  CAS  PubMed  Google Scholar 

  44. Andersson ER, Sandberg R, Lendahl U. Notch signaling: simplicity in design, versatility in function. Development. 2011;138(17):3593–612.

    Article  CAS  PubMed  Google Scholar 

  45. Timmerman LA, et al. Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev. 2004;18(1):99–115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Garg V, et al. Mutations in NOTCH1 cause aortic valve disease. Nature. 2005;437(7056):270–4.

    Article  CAS  PubMed  Google Scholar 

  47. Marvin MJ, et al. Inhibition of Wnt activity induces heart formation from posterior mesoderm. Genes Dev. 2001;15(3):316–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Hurlstone AF, et al. The Wnt/beta-catenin pathway regulates cardiac valve formation. Nature. 2003;425(6958):633–7.

    Article  CAS  PubMed  Google Scholar 

  49. Liebner S, et al. Beta-catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse. J Cell Biol. 2004;166(3):359–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Gitler AD, et al. Molecular markers of cardiac endocardial cushion development. Dev Dyn. 2003;228(4):643–50.

    Article  CAS  PubMed  Google Scholar 

  51. Person AD, et al. Frzb modulates Wnt-9a-mediated beta-catenin signaling during avian atrioventricular cardiac cushion development. Dev Biol. 2005;278(1):35–48.

    Article  CAS  PubMed  Google Scholar 

  52. Ma L, et al. Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning. Development. 2005;132(24):5601–11.

    Article  CAS  PubMed  Google Scholar 

  53. Delot EC. Control of endocardial cushion and cardiac valve maturation by BMP signaling pathways. Mol Genet Metab. 2003;80(1–2):27–35.

    Article  CAS  PubMed  Google Scholar 

  54. Liu W, et al. Bmp4 signaling is required for outflow-tract septation and branchial-arch artery remodeling. Proc Natl Acad Sci U S A. 2004;101(13):4489–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kim RY, Robertson EJ, Solloway MJ. Bmp6 and Bmp7 are required for cushion formation and septation in the developing mouse heart. Dev Biol. 2001;235(2):449–66.

    Article  CAS  PubMed  Google Scholar 

  56. Kaden JJ, et al. Expression of bone sialoprotein and bone morphogenetic protein-2 in calcific aortic stenosis. J Heart Valve Dis. 2004;13(4):560–6.

    PubMed  Google Scholar 

  57. Winnier G, et al. Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev. 1995;9(17):2105–16.

    Article  CAS  PubMed  Google Scholar 

  58. Solloway MJ, Robertson EJ. Early embryonic lethality in Bmp5;Bmp7 double mutant mice suggests functional redundancy within the 60A subgroup. Development. 1999;126(8):1753–68.

    CAS  PubMed  Google Scholar 

  59. Inai K, et al. BMP-2 induces cell migration and periostin expression during atrioventricular valvulogenesis. Dev Biol. 2008;315(2):383–96.

    Article  CAS  PubMed  Google Scholar 

  60. Shelton EL, Yutzey KE. Tbx20 regulation of endocardial cushion cell proliferation and extracellular matrix gene expression. Dev Biol. 2007;302(2):376–88.

    Article  CAS  PubMed  Google Scholar 

  61. Shelton EL, Yutzey KE. Twist1 function in endocardial cushion cell proliferation, migration, and differentiation during heart valve development. Dev Biol. 2008;317(1):282–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Lincoln J, Alfieri CM, Yutzey KE. BMP and FGF regulatory pathways control cell lineage diversification of heart valve precursor cells. Dev Biol. 2006;292(2):292–302.

    Article  PubMed  CAS  Google Scholar 

  63. Zhao B, et al. BMP and FGF regulatory pathways in semilunar valve precursor cells. Dev Dyn. 2007;236(4):971–80.

    Article  CAS  PubMed  Google Scholar 

  64. Brown CB, et al. Antibodies to the type II TGFbeta receptor block cell activation and migration during atrioventricular cushion transformation in the heart. Dev Biol. 1996;174(2):248–57.

    Article  CAS  PubMed  Google Scholar 

  65. Azhar M, et al. Ligand-specific function of transforming growth factor beta in epithelial-mesenchymal transition in heart development. Dev Dyn. 2009;238(2):431–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Person AD, Klewer SE, Runyan RB. Cell biology of cardiac cushion development. Int Rev Cytol. 2005;243:287–335.

    Article  CAS  PubMed  Google Scholar 

  67. Molin DG, et al. Expression patterns of Tgfbeta1-3 associate with myocardialisation of the outflow tract and the development of the epicardium and the fibrous heart skeleton. Dev Dyn. 2003;227(3):431–44.

    Article  CAS  PubMed  Google Scholar 

  68. Beffagna G, et al. Regulatory mutations in transforming growth factor-beta3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1. Cardiovasc Res. 2005;65(2):366–73.

    Article  CAS  PubMed  Google Scholar 

  69. Hu BC, et al. The association between transforming growth factor beta3 polymorphisms and left ventricular structure in hypertensive subjects. Clin Chim Acta. 2010;411(7–8):558–62.

    Article  CAS  PubMed  Google Scholar 

  70. Conway SJ, Doetschman T, Azhar M. The inter-relationship of periostin, TGF beta, and BMP in heart valve development and valvular heart diseases. ScientificWorldJournal. 2011;11:1509–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Chen B, et al. Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis. Nat Genet. 2000;24(3):296–9.

    Article  CAS  PubMed  Google Scholar 

  72. Erickson SL, et al. ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2-and heregulin-deficient mice. Development. 1997;124(24):4999–5011.

    CAS  PubMed  Google Scholar 

  73. Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002;39(12):1890–900.

    Article  PubMed  Google Scholar 

  74. Loffredo CA. Epidemiology of cardiovascular malformations: prevalence and risk factors. Am J Med Genet. 2000;97(4):319–25.

    Article  CAS  PubMed  Google Scholar 

  75. Huang JB, et al. Molecular mechanisms of congenital heart disease. Cardiovasc Pathol. 2010;19(5):e183–93.

    Article  CAS  PubMed  Google Scholar 

  76. Zeng Q, et al. Notch1 promotes the pro-osteogenic response of human aortic valve interstitial cells via modulation of ERK1/2 and nuclear factor-kappaB activation. Arterioscler Thromb Vasc Biol. 2013;33(7):1580–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Fukuda D, et al. Notch ligand delta-like 4 blockade attenuates atherosclerosis and metabolic disorders. Proc Natl Acad Sci U S A. 2012;109(27):E1868–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Wang J, Greene SB, Martin JF. BMP signaling in congenital heart disease: new developments and future directions. Birth Defects Res A Clin Mol Teratol. 2011;91(6):441–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Yang X, et al. Bone morphogenic protein 2 induces Runx2 and osteopontin expression in human aortic valve interstitial cells: role of Smad1 and extracellular signal-regulated kinase 1/2. J Thorac Cardiovasc Surg. 2009;138(4):1008–15.

    Article  CAS  PubMed  Google Scholar 

  80. Mohler ER 3rd, et al. Bone formation and inflammation in cardiac valves. Circulation. 2001;103(11):1522–8.

    Article  PubMed  Google Scholar 

  81. Ankeny RF, et al. Preferential activation of SMAD1/5/8 on the fibrosa endothelium in calcified human aortic valves—association with low BMP antagonists and SMAD6. PLoS One. 2011;6(6):e20969.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. ten Dijke P, Arthur HM. Extracellular control of TGFbeta signalling in vascular development and disease. Nat Rev Mol Cell Biol. 2007;8(11):857–69.

    Article  PubMed  CAS  Google Scholar 

  83. Pardali E, Goumans MJ, ten Dijke P. Signaling by members of the TGF-beta family in vascular morphogenesis and disease. Trends Cell Biol. 2010;20(9):556–67.

    Article  CAS  PubMed  Google Scholar 

  84. Doetschman T, et al. Transforming growth factor beta signaling in adult cardiovascular diseases and repair. Cell Tissue Res. 2012;347(1):203–23.

    Article  CAS  PubMed  Google Scholar 

  85. Benke K, et al. The role of transforming growth factor-beta in Marfan syndrome. Cardiol J. 2013;20(3):227–34.

    Article  PubMed  Google Scholar 

  86. Koch W, et al. Association of transforming growth factor-beta1 gene polymorphisms with myocardial infarction in patients with angiographically proven coronary heart disease. Arterioscler Thromb Vasc Biol. 2006;26(5):1114–9.

    Article  CAS  PubMed  Google Scholar 

  87. Yokota M, et al. Association of a T29-->C polymorphism of the transforming growth factor-beta1 gene with genetic susceptibility to myocardial infarction in Japanese. Circulation. 2000;101(24):2783–7.

    Article  CAS  PubMed  Google Scholar 

  88. Clark-Greuel JN, et al. Transforming growth factor-beta1 mechanisms in aortic valve calcification: increased alkaline phosphatase and related events. Ann Thorac Surg. 2007;83(3):946–53.

    Article  PubMed  Google Scholar 

  89. Walker GA, et al. Valvular myofibroblast activation by transforming growth factor-beta: implications for pathological extracellular matrix remodeling in heart valve disease. Circ Res. 2004;95(3):253–60.

    Article  CAS  PubMed  Google Scholar 

  90. Liu AC, Joag VR, Gotlieb AI. The emerging role of valve interstitial cell phenotypes in regulating heart valve pathobiology. Am J Pathol. 2007;171(5):1407–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Chen JH, et al. Beta-catenin mediates mechanically regulated, transforming growth factor-beta1-induced myofibroblast differentiation of aortic valve interstitial cells. Arterioscler Thromb Vasc Biol. 2011;31(3):590–7.

    Article  CAS  PubMed  Google Scholar 

  92. Hutcheson JD, et al. Serotonin receptors and heart valve disease—it was meant 2B. Pharmacol Ther. 2011;132(2):146–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Jian B, et al. Serotonin mechanisms in heart valve disease I: serotonin-induced up-regulation of transforming growth factor-beta1 via G-protein signal transduction in aortic valve interstitial cells. Am J Pathol. 2002;161(6):2111–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Xu J, et al. Serotonin mechanisms in heart valve disease II: the 5-HT2 receptor and its signaling pathway in aortic valve interstitial cells. Am J Pathol. 2002;161(6):2209–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Nebigil CG, et al. Ablation of serotonin 5-HT(2B) receptors in mice leads to abnormal cardiac structure and function. Circulation. 2001;103(24):2973–9.

    Article  CAS  PubMed  Google Scholar 

  96. Fabre A, et al. Modulation of bleomycin-induced lung fibrosis by serotonin receptor antagonists in mice. Eur Respir J. 2008;32(2):426–36.

    Article  CAS  PubMed  Google Scholar 

  97. Vermot J, et al. Reversing blood flows act through klf2a to ensure normal valvulogenesis in the developing heart. PLoS Biol. 2009;7(11):e1000246.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Gordon WR, et al. Mechanical Allostery: evidence for a force requirement in the proteolytic activation of notch. Dev Cell. 2015;33(6):729–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Yanagisawa H, et al. Dual genetic pathways of endothelin-mediated intercellular signaling revealed by targeted disruption of endothelin converting enzyme-1 gene. Development. 1998;125(5):825–36.

    CAS  PubMed  Google Scholar 

  100. Kurihara Y, et al. Aortic arch malformations and ventricular septal defect in mice deficient in endothelin-1. J Clin Invest. 1995;96(1):293–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Yalcin HC, et al. Hemodynamic patterning of the avian atrioventricular valve. Dev Dyn. 2011;240(1):23–35.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Sun L, Sucosky P. Bone morphogenetic protein-4 and transforming growth factor-beta1 mechanisms in acute valvular response to supra-physiologic hemodynamic stresses. World J Cardiol. 2015;7(6):331–43.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Fisher CI, Chen J, Merryman WD. Calcific nodule morphogenesis by heart valve interstitial cells is strain dependent. Biomech Model Mechanobiol. 2013;12(1):5–17.

    Article  PubMed  Google Scholar 

  104. Balachandran K, et al. Elevated cyclic stretch and serotonin result in altered aortic valve remodeling via a mechanosensitive 5-HT(2A) receptor-dependent pathway. Cardiovasc Pathol. 2012;21(3):206–13.

    Article  CAS  PubMed  Google Scholar 

  105. Balachandran K, et al. Aortic valve cyclic stretch causes increased remodeling activity and enhanced serotonin receptor responsiveness. Ann Thorac Surg. 2011;92(1):147–53.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Liang YJ, et al. Mechanical stress enhances serotonin 2B receptor modulating brain natriuretic peptide through nuclear factor-kappaB in cardiomyocytes. Cardiovasc Res. 2006;72(2):303–12.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biomedical Engineering, University of Arkansas, Fayetteville, AR, USA

    Ishita Tandon, Ngoc Thien Lam & Kartik Balachandran

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  1. Ishita Tandon
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  2. Ngoc Thien Lam
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  3. Kartik Balachandran
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Correspondence to Kartik Balachandran .

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Editors and Affiliations

  1. The Oden Institute and the Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA

    Michael S. Sacks

  2. The Department of Bioengineering, The University of Texas at Arlington, Arlington, TX, USA

    Jun Liao

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Tandon, I., Lam, N.T., Balachandran, K. (2018). Mechanical Mediation of Signaling Pathways in Heart Valve Development and Disease. In: Sacks, M., Liao, J. (eds) Advances in Heart Valve Biomechanics. Springer, Cham. https://doi.org/10.1007/978-3-030-01993-8_10

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