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Annual Review of Physiology

Volume 79, 2017

Developmental Mechanisms of Aortic Valve Malformation and Disease

Abstract

Normal aortic valves are composed of valve endothelial cells (VECs) and valve interstitial cells (VICs). VICs are the major cell population and have distinct embryonic origins in the endocardium and cardiac neural crest cells. Cell signaling between the VECs and VICs plays critical roles in aortic valve morphogenesis. Disruption of major cell signaling pathways results in aortic valve malformations, including bicuspid aortic valve (BAV). BAV is a common congenital heart valve disease that may lead to calcific aortic valve disease (CAVD), but there is currently no effective medical treatment for this beyond surgical replacement. Mouse and human studies have identified causative gene mutations for BAV and CAVD via disrupted VEC to VIC signaling. Future studies on the developmental signaling mechanisms underlying aortic valve malformations and the pathogenesis of CAVD using genetically modified mouse models and patient-induced pluripotent stem cells may identify new effective therapeutic targets for the disease.

Keyword(s): animal model, bicuspid aortic valve, cell signaling, heart valve development, valve endocardial cell, valve interstitial cell
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/content/journals/10.1146/annurev-physiol-022516-034001
2017-02-10
2024-04-23
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Literature Cited

  1. Brickner ME, Hillis LD, Lange RA. 1.  2000. Congenital heart disease in adults. First of two parts. N. Engl. J. Med. 342:256–63 [Google Scholar]
  2. Caira FC, Stock SR, Gleason TG, McGee EC, Huang J. 2.  et al. 2006. Human degenerative valve disease is associated with up-regulation of low-density lipoprotein receptor-related protein 5 receptor-mediated bone formation. J. Am. Coll. Cardiol. 47:1707–12 [Google Scholar]
  3. Erbel R, Aboyans V, Boileau C, Bossone E, Bartolomeo RD. 3.  et al. 2014. 2014 ESC guidelines on the diagnosis and treatment of aortic diseases. Eur. Heart J. 35:2873–926 [Google Scholar]
  4. Yutzey KE, Demer LL, Body SC, Huggins GS, Towler DA. 4.  et al. 2014. Calcific aortic valve disease: a consensus summary from the alliance of investigators on calcific aortic valve disease. Arterioscler. Thromb. Vasc. Biol. 34:2387–93 [Google Scholar]
  5. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd. 5.  et al. 2014. 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. Circulation 129:e521–643 [Google Scholar]
  6. Hoffman JI, Kaplan S. 6.  2002. The incidence of congenital heart disease. J. Am. Coll. Cardiol. 39:1890–900 [Google Scholar]
  7. Runyan RB, Markwald RR. 7.  1983. Invasion of mesenchyme into three-dimensional collagen gels: a regional and temporal analysis of interaction in embryonic heart tissue. Dev. Biol. 95:108–14 [Google Scholar]
  8. Eisenberg LM, Markwald RR. 8.  1995. Molecular regulation of atrioventricular valvuloseptal morphogenesis. Circ. Res. 77:1–6 [Google Scholar]
  9. de Lange FJ, Moorman AF, Anderson RH, Manner J, Soufan AT. 9.  et al. 2004. Lineage and morphogenetic analysis of the cardiac valves. Circ. Res. 95:645–54 [Google Scholar]
  10. Gustafsson E, Brakebusch C, Hietanen K, Fassler R. 10.  2001. Tie-1-directed expression of Cre recombinase in endothelial cells of embryoid bodies and transgenic mice. J. Cell Sci. 114:671–76 [Google Scholar]
  11. Jiang X, Choudhary B, Merki E, Chien KR, Maxson RE, Sucov HM. 11.  2002. Normal fate and altered function of the cardiac neural crest cell lineage in retinoic acid receptor mutant embryos. Mech. Dev. 117:115–22 [Google Scholar]
  12. Armstrong EJ, Bischoff J. 12.  2004. Heart valve development: endothelial cell signaling and differentiation. Circ. Res. 95:459–70 [Google Scholar]
  13. Hinton RB, Yutzey KE. 13.  2011. Heart valve structure and function in development and disease. Annu. Rev. Physiol. 73:29–46 [Google Scholar]
  14. Lin CJ, Lin CY, Chen CH, Zhou B, Chang CP. 14.  2012. Partitioning the heart: mechanisms of cardiac septation and valve development. Development 139:3277–99 [Google Scholar]
  15. Lincoln J, Yutzey KE. 15.  2011. Molecular and developmental mechanisms of congenital heart valve disease. Birth Defects Res. Clin. Mol. Teratol. 91:526–34 [Google Scholar]
  16. Wang Y, Wu B, Farrar E, Lui W, Lu P. 16.  et al. 2015. Notch-Tnf signalling is required for development and homeostasis of arterial valves. Eur. Heart J. In press. https://doi.org/10.1093/eurheartj/ehv520
  17. Huk DJ, Austin BF, Horne TE, Hinton RB, Ray WC. 17.  et al. 2016. Valve endothelial cell-derived Tgfβ1 signaling promotes nuclear localization of Sox9 in interstitial cells associated with attenuated calcification. Arterioscler. Thromb. Vasc. Biol. 36:328–38 [Google Scholar]
  18. MacGrogan D, D'Amato G, Travisano S, Martinez-Poveda B, de Luxan G. 18.  et al. 2016. Sequential ligand-dependent notch signaling activation regulates valve primordium formation and morphogenesis. Circ. Res. 118:1480–97 [Google Scholar]
  19. Luxan G, D'Amato G, MacGrogan D, de la Pompa JL. 19.  2016. Endocardial notch signaling in cardiac development and disease. Circ. Res. 118:e1–18 [Google Scholar]
  20. Garg V, Muth AN, Ransom JF, Schluterman MK, Barnes R. 20.  et al. 2005. Mutations in NOTCH1 cause aortic valve disease. Nature 437:270–74 [Google Scholar]
  21. McBride KL, Riley MF, Zender GA, Fitzgerald-Butt SM, Towbin JA. 21.  et al. 2008. NOTCH1 mutations in individuals with left ventricular outflow tract malformations reduce ligand-induced signaling. Hum. Mol. Genet. 17:2886–93 [Google Scholar]
  22. Lawson KA, Meneses JJ, Pedersen RA. 22.  1991. Clonal analysis of epiblast fate during germ layer formation in the mouse embryo. Development 113:891–911 [Google Scholar]
  23. Tam PP, Parameswaran M, Kinder SJ, Weinberger RP. 23.  1997. The allocation of epiblast cells to the embryonic heart and other mesodermal lineages: the role of ingression and tissue movement during gastrulation. Development 124:1631–42 [Google Scholar]
  24. Vincent SD, Buckingham ME. 24.  2010. How to make a heart: the origin and regulation of cardiac progenitor cells. Curr. Top. Dev. Biol. 90:1–41 [Google Scholar]
  25. Abu-Issa R, Kirby ML. 25.  2007. Heart field: from mesoderm to heart tube. Annu. Rev. Cell Dev. Biol. 23:45–68 [Google Scholar]
  26. Bruneau BG. 26.  2008. The developmental genetics of congenital heart disease. Nature 451:943–48 [Google Scholar]
  27. Kelly RG, Brown NA, Buckingham ME. 27.  2001. The arterial pole of the mouse heart forms from Fgf10-expressing cells in pharyngeal mesoderm. Dev. Cell 1:435–40 [Google Scholar]
  28. Mjaatvedt CH, Nakaoka T, Moreno-Rodriguez R, Norris RA, Kern MJ. 28.  et al. 2001. The outflow tract of the heart is recruited from a novel heart-forming field. Dev. Biol. 238:97–109 [Google Scholar]
  29. Waldo KL, Kumiski DH, Wallis KT, Stadt HA, Hutson MR. 29.  et al. 2001. Conotruncal myocardium arises from a secondary heart field. Development 128:3179–88 [Google Scholar]
  30. Cai CL, Liang X, Shi Y, Chu PH, Pfaff SL. 30.  et al. 2003. Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Dev. Cell 5:877–89 [Google Scholar]
  31. Markwald R, Eisenberg C, Eisenberg L, Trusk T, Sugi Y. 31.  1996. Epithelial-mesenchymal transformations in early avian heart development. Acta Anat. 156:173–86 [Google Scholar]
  32. Ma L, Lu MF, Schwartz RJ, Martin JF. 32.  2005. Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning. Development 132:5601–11 [Google Scholar]
  33. Person AD, Klewer SE, Runyan RB. 33.  2005. Cell biology of cardiac cushion development. Int. Rev. Cytol. 243:287–335 [Google Scholar]
  34. Lincoln J, Alfieri CM, Yutzey KE. 34.  2004. Development of heart valve leaflets and supporting apparatus in chicken and mouse embryos. Dev. Dyn. 230:239–50 [Google Scholar]
  35. Schroeder JA, Jackson LF, Lee DC, Camenisch TD. 35.  2003. Form and function of developing heart valves: coordination by extracellular matrix and growth factor signaling. J. Mol. Med. 81:392–403 [Google Scholar]
  36. Butcher JT, McQuinn TC, Sedmera D, Turner D, Markwald RR. 36.  2007. Transitions in early embryonic atrioventricular valvular function correspond with changes in cushion biomechanics that are predictable by tissue composition. Circ. Res. 100:1503–11 [Google Scholar]
  37. Snarr BS, Wirrig EE, Phelps AL, Trusk TC, Wessels A. 37.  2007. A spatiotemporal evaluation of the contribution of the dorsal mesenchymal protrusion to cardiac development. Dev. Dyn. 236:1287–94 [Google Scholar]
  38. Yalcin HC, Shekhar A, McQuinn TC, Butcher JT. 38.  2011. Hemodynamic patterning of the avian atrioventricular valve. Dev. Dyn. 240:23–35 [Google Scholar]
  39. Butcher JT, McQuinn TC, Sedmera D, Turner D, Markwald RR. 39.  2007. Transitions in early embryonic atrioventricular valvular function correspond with changes in cushion biomechanics that are predictable by tissue composition. Circ. Res. 100:1503–11 [Google Scholar]
  40. Qayyum SR, Webb S, Anderson RH, Verbeek FJ, Brown NA, Richardson MK. 40.  2001. Septation and valvar formation in the outflow tract of the embryonic chick heart. Anat. Rec. 264:273–83 [Google Scholar]
  41. Webb S, Qayyum SR, Anderson RH, Lamers WH, Richardson MK. 41.  2003. Septation and separation within the outflow tract of the developing heart. J. Anat. 202:327–42 [Google Scholar]
  42. Anderson RH, Webb S, Brown NA, Lamers W, Moorman A. 42.  2003. Development of the heart: (3) formation of the ventricular outflow tracts, arterial valves, and intrapericardial arterial trunks. Heart 89:1110–18 [Google Scholar]
  43. Kirby ML, Gale TF, Stewart DE. 43.  1983. Neural crest cells contribute to normal aorticopulmonary septation. Science 220:1059–61 [Google Scholar]
  44. Jain R, Engleka KA, Rentschler SL, Manderfield LJ, Li L. 44.  et al. 2011. Cardiac neural crest orchestrates remodeling and functional maturation of mouse semilunar valves. J. Clin. Investig. 121:422–30 [Google Scholar]
  45. Wu B, Wang Y, Lui W, Langworthy M, Tompkins KL. 45.  et al. 2011. Nfatc1 coordinates valve endocardial cell lineage development required for heart valve formation. Circ. Res. 109:183–92 [Google Scholar]
  46. Wu B, Baldwin HS, Zhou B. 46.  2013. Nfatc1 directs the endocardial progenitor cells to make heart valve primordium. Trends Cardiovasc. Med. 23:294–300 [Google Scholar]
  47. Aikawa E, Whittaker P, Farber M, Mendelson K, Padera RF. 47.  et al. 2006. Human semilunar cardiac valve remodeling by activated cells from fetus to adult: implications for postnatal adaptation, pathology, and tissue engineering. Circulation 113:1344–52 [Google Scholar]
  48. Hinton RB Jr., Lincoln J, Deutsch GH, Osinska H, Manning PB. 48.  et al. 2006. Extracellular matrix remodeling and organization in developing and diseased aortic valves. Circ. Res. 98:1431–38 [Google Scholar]
  49. Hurle JM, Colvee E, Blanco AM. 49.  1980. Development of mouse semilunar valves. Anat. Embryol. 160:83–91 [Google Scholar]
  50. Verzi MP, McCulley DJ, De Val S, Dodou E, Black BL. 50.  2005. The right ventricle, outflow tract, and ventricular septum comprise a restricted expression domain within the secondary/anterior heart field. Dev. Biol. 287:134–45 [Google Scholar]
  51. Snarr BS, Kern CB, Wessels A. 51.  2008. Origin and fate of cardiac mesenchyme. Dev. Dyn. 237:2804–19 [Google Scholar]
  52. Nakamura T, Colbert MC, Robbins J. 52.  2006. Neural crest cells retain multipotential characteristics in the developing valves and label the cardiac conduction system. Circ. Res. 98:1547–54 [Google Scholar]
  53. Hajdu Z, Romeo SJ, Fleming PA, Markwald RR, Visconti RP, Drake CJ. 53.  2011. Recruitment of bone marrow-derived valve interstitial cells is a normal homeostatic process. J. Mol. Cell. Cardiol. 51:955–65 [Google Scholar]
  54. Baldwin HS, Lloyd TR, Solursh M. 54.  1994. Hyaluronate degradation affects ventricular function of the early postlooped embryonic rat heart in situ. Circ. Res. 74:244–52 [Google Scholar]
  55. Camenisch TD, Schroeder JA, Bradley J, Klewer SE, McDonald JA. 55.  2002. Heart-valve mesenchyme formation is dependent on hyaluronan-augmented activation of ErbB2-ErbB3 receptors. Nat. Med. 8:850–55 [Google Scholar]
  56. Dor Y, Camenisch TD, Itin A, Fishman GI, McDonald JA. 56.  et al. 2001. A novel role for VEGF in endocardial cushion formation and its potential contribution to congenital heart defects. Development 128:1531–38 [Google Scholar]
  57. Chang CP, Neilson JR, Bayle JH, Gestwicki JE, Kuo A. 57.  et al. 2004. A field of myocardial-endocardial NFAT signaling underlies heart valve morphogenesis. Cell 118:649–63 [Google Scholar]
  58. Hurlstone AF, Haramis AP, Wienholds E, Begthel H, Korving J. 58.  et al. 2003. The Wnt/β-catenin pathway regulates cardiac valve formation. Nature 425:633–37 [Google Scholar]
  59. Liebner S, Cattelino A, Gallini R, Rudini N, Iurlaro M. 59.  et al. 2004. β-Catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse. J. Cell Biol. 166:359–67 [Google Scholar]
  60. Timmerman LA, Grego-Bessa J, Raya A, Bertran E, Perez-Pomares JM. 60.  et al. 2004. Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev 18:99–115 [Google Scholar]
  61. Niessen K, Fu Y, Chang L, Hoodless PA, McFadden D, Karsan A. 61.  2008. Slug is a direct Notch target required for initiation of cardiac cushion cellularization. J. Cell Biol. 182:315–25 [Google Scholar]
  62. Luna-Zurita L, Prados B, Grego-Bessa J, Luxán G, del Monte G. 62.  et al. 2010. Integration of a Notch-dependent mesenchymal gene program and Bmp2-driven cell invasiveness regulates murine cardiac valve formation. J. Clin. Investig. 120:3493–507 [Google Scholar]
  63. Wang Y, Wu B, Chamberlain AA, Lui W, Koirala P. 63.  et al. 2013. Endocardial to myocardial Notch-Wnt-Bmp axis regulates early heart valve development. PLOS ONE 8:e60244 [Google Scholar]
  64. Cai X, Zhang W, Hu J, Zhang L, Sultana N. 64.  et al. 2013. Tbx20 acts upstream of Wnt signaling to regulate endocardial cushion formation and valve remodeling during mouse cardiogenesis. Development 140:3176–87 [Google Scholar]
  65. Stankunas K, Ma GK, Kuhnert FJ, Kuo CJ, Chang CP. 65.  2010. VEGF signaling has distinct spatiotemporal roles during heart valve development. Dev. Biol. 347:325–36 [Google Scholar]
  66. Bosada FM, Devasthali V, Jones KA, Stankunas K. 66.  2016. Wnt/β-catenin signaling enables developmental transitions during valvulogenesis. Development 143:1041–54 [Google Scholar]
  67. Lincoln J, Kist R, Scherer G, Yutzey KE. 67.  2007. Sox9 is required for precursor cell expansion and extracellular matrix organization during mouse heart valve development. Dev. Biol. 305:120–32 [Google Scholar]
  68. Chakraborty S, Wirrig EE, Hinton RB, Merrill WH, Spicer DB, Yutzey KE. 68.  2010. Twist1 promotes heart valve cell proliferation and extracellular matrix gene expression during development in vivo and is expressed in human diseased aortic valves. Dev. Biol. 347:167–79 [Google Scholar]
  69. Chakraborty S, Combs MD, Yutzey KE. 69.  2010. Transcriptional regulation of heart valve progenitor cells. Pediatr. Cardiol. 31:414–21 [Google Scholar]
  70. Jain R, Rentschler S, Epstein JA. 70.  2010. Notch and cardiac outflow tract development. Ann. N.Y. Acad. Sci. 1188:184–90 [Google Scholar]
  71. Combs MD, Yutzey KE. 71.  2009. VEGF and RANKL regulation of NFATc1 in heart valve development. Circ. Res. 105:565–74 [Google Scholar]
  72. Lincoln J, Lange AW, Yutzey KE. 72.  2006. Hearts and bones: shared regulatory mechanisms in heart valve, cartilage, tendon, and bone development. Dev. Biol. 294:292–302 [Google Scholar]
  73. Lincoln J, Alfieri CM, Yutzey KE. 73.  2006. BMP and FGF regulatory pathways control cell lineage diversification of heart valve precursor cells. Dev. Biol. 292:290–302 [Google Scholar]
  74. Chiu YN, Norris RA, Mahler G, Recknagel A, Butcher JT. 74.  2010. Transforming growth factor β, bone morphogenetic protein, and vascular endothelial growth factor mediate phenotype maturation and tissue remodeling by embryonic valve progenitor cells: relevance for heart valve tissue engineering. Tissue Eng. A 16:3375–83 [Google Scholar]
  75. Alfieri CM, Cheek J, Chakraborty S, Yutzey KE. 75.  2010. Wnt signaling in heart valve development and osteogenic gene induction. Dev. Biol. 338:127–35 [Google Scholar]
  76. Cheek JD, Wirrig EE, Alfieri CM, James JF, Yutzey KE. 76.  2012. Differential activation of valvulogenic, chondrogenic, and osteogenic pathways in mouse models of myxomatous and calcific aortic valve disease. J. Mol. Cell. Cardiol. 52:689–700 [Google Scholar]
  77. Galvin KM, Donovan MJ, Lynch CA, Meyer RI, Paul RJ. 77.  et al. 2000. A role for Smad6 in development and homeostasis of the cardiovascular system. Nat. Genet. 24:171–74 [Google Scholar]
  78. Groenendijk BC, Hierck BP, Gittenberger-De Groot AC, Poelmann RE. 78.  2004. Development-related changes in the expression of shear stress responsive genes KLF-2, ET-1, and NOS-3 in the developing cardiovascular system of chicken embryos. Dev. Dyn. 230:57–68 [Google Scholar]
  79. Butcher JT, Markwald RR. 79.  2007. Valvulogenesis: the moving target. Philos. Trans. R. Soc. B 362:1489–503 [Google Scholar]
  80. Buskohl PR, Gould RA, Butcher JT. 80.  2012. Quantification of embryonic atrioventricular valve biomechanics during morphogenesis. J. Biomech. 45:895–902 [Google Scholar]
  81. Butcher JT, Nerem RM. 81.  2007. Valvular endothelial cells and the mechanoregulation of valvular pathology. Philos. Trans. R. Soc. B 362:1445–57 [Google Scholar]
  82. Vermot J, Forouhar AS, Liebling M, Wu D, Plummer D. 82.  et al. 2009. Reversing blood flows act through klf2a to ensure normal valvulogenesis in the developing heart. PLOS Biol 7:e1000246 [Google Scholar]
  83. Hove JR, Koster RW, Forouhar AS, Acevedo-Bolton G, Fraser SE, Gharib M. 83.  2003. Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis. Nature 421:172–77 [Google Scholar]
  84. Otto CM, Kuusisto J, Reichenbach DD, Gown AM, O'Brien KD. 84.  1994. Characterization of the early lesion of ‘degenerative’ valvular aortic stenosis. Histological and immunohistochemical studies. Circulation 90:844–53 [Google Scholar]
  85. Butcher JT, Penrod AM, García AJ, Nerem RM. 85.  2004. Unique morphology and focal adhesion development of valvular endothelial cells in static and fluid flow environments. Arterioscler. Thromb. Vasc. Biol. 24:1429–34 [Google Scholar]
  86. Imberti B, Seliktar D, Nerem RM, Remuzzi A. 86.  2002. The response of endothelial cells to fluid shear stress using a co-culture model of the arterial wall. Endothelium 9:11–23 [Google Scholar]
  87. Wang N, Butler JP, Ingber DE. 87.  1993. Mechanotransduction across the cell surface and through the cytoskeleton. Science 260:1124–27 [Google Scholar]
  88. Misfeld M, Morrison K, Sievers H, Yacoub MH, Chester AH. 88.  2002. Localization of immunoreactive endothelin and characterization of its receptors in aortic cusps. J. Heart Valve Dis. 11:472–77 [Google Scholar]
  89. Farivar RS, Cohn LH, Soltesz EG, Mihaljevic T, Rawn JD, Byrne JG. 89.  2003. Transcriptional profiling and growth kinetics of endothelium reveals differences between cells derived from porcine aorta versus aortic valve. Eur. J. Cardiothorac. Surg. 24:527–34 [Google Scholar]
  90. Butcher JT, Tressel S, Johnson T, Turner D, Sorescu G. 90.  et al. 2006. Transcriptional profiles of valvular and vascular endothelial cells reveal phenotypic differences: influence of shear stress. Arterioscler. Thromb. Vasc. Biol. 26:69–77 [Google Scholar]
  91. Rabkin E, Aikawa M, Stone JR, Fukumoto Y, Libby P, Schoen FJ. 91.  2001. Activated interstitial myofibro-blasts express catabolic enzymes and mediate matrix remodeling in myxomatous heart valves. Circulation 104:2525–32 [Google Scholar]
  92. Rabkin-Aikawa E, Farber M, Aikawa M, Schoen FJ. 92.  2004. Dynamic and reversible changes of interstitial cell phenotype during remodeling of cardiac valves. J. Heart Valve Dis. 13:841–47 [Google Scholar]
  93. Osman L, Yacoub MH, Latif N, Amrani M, Chester AH. 93.  2006. Role of human valve interstitial cells in valve calcification and their response to atorvastatin. Circulation 114:I547–52 [Google Scholar]
  94. Liu AC, Joag VR, Gotlieb AI. 94.  2007. The emerging role of valve interstitial cell phenotypes in regulating heart valve pathobiology. Am. J. Pathol. 171:1407–18 [Google Scholar]
  95. Bowen CJ, Zhou J, Sung DC, Butcher JT. 95.  2015. Cadherin-11 coordinates cellular migration and extracellular matrix remodeling during aortic valve maturation. Dev. Biol. 407:145–57 [Google Scholar]
  96. Gould RA, Yalcin HC, MacKay JL, Sauls K, Norris R. 96.  et al. 2016. Cyclic mechanical loading is essential for Rac1-mediated elongation and remodeling of the embryonic mitral valve. Curr Biol 26:27–37 [Google Scholar]
  97. Sung D, Bowen C, Vaidya K, Zhou J, Ciapurin N, Recknagel A. 97.  et al. 2016. Cadherin-11 overexpression induces extracellular matrix remodeling and calcification in mature aortic valves. Arterioscler. Thromb. Vasc. Biol. 361627–37
  98. Grande KJ, Cochran RP, Reinhall PG, Kunzelman KS. 98.  1998. Stress variations in the human aortic root and valve: the role of anatomic asymmetry. Ann. Biomed. Eng. 26:534–45 [Google Scholar]
  99. Carruthers CA, Alfieri CM, Joyce EM, Watkins SC, Yutzey KE, Sacks MS. 99.  2012. Gene expression and collagen fiber micromechanical interactions of the semilunar heart valve interstitial cell. Cell. Mol. Bioeng. 5:254–65 [Google Scholar]
  100. Kershaw JD, Misfeld M, Sievers HH, Yacoub MH, Chester AH. 100.  2004. Specific regional and directional contractile responses of aortic cusp tissue. J. Heart Valve Dis. 13:798–803 [Google Scholar]
  101. Schoen FJ. 101.  1997. Aortic valve structure-function correlations: role of elastic fibers no longer a stretch of the imagination. J. Heart Valve Dis. 6:1–6 [Google Scholar]
  102. Schoen FJ. 102.  2008. Evolving concepts of cardiac valve dynamics: the continuum of development, functional structure, pathobiology, and tissue engineering. Circulation 118:1864–80 [Google Scholar]
  103. Latif N, Sarathchandra P, Taylor PM, Antoniw J, Yacoub MH. 103.  2005. Molecules mediating cell–ECM and cell–cell communication in human heart valves. Cell Biochem. Biophys. 43:275–87 [Google Scholar]
  104. Li DY, Brooke B, Davis EC, Mecham RP, Sorensen LK. 104.  et al. 1998. Elastin is an essential determinant of arterial morphogenesis. Nature 393:276–80 [Google Scholar]
  105. Li DY, Faury G, Taylor DG, Davis EC, Boyle WA. 105.  et al. 1998. Novel arterial pathology in mice and humans hemizygous for elastin. J. Clin. Investig. 102:1783–87 [Google Scholar]
  106. Hinton RB, Adelman-Brown J, Witt S, Krishnamurthy VK, Osinska H. 106.  et al. 2010. Elastin haploinsufficiency results in progressive aortic valve malformation and latent valve disease in a mouse model. Circ. Res. 107:549–57 [Google Scholar]
  107. Otto CM. 107.  2006. Valvular aortic stenosis: disease severity and timing of intervention. J. Am. Coll. Cardiol. 47:2141–51 [Google Scholar]
  108. Sacks MS, Merryman WD, Schmidt DE. 108.  2009. On the biomechanics of heart valve function. J. Biomech. 42:1804–24 [Google Scholar]
  109. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. 109.  2006. Burden of valvular heart diseases: a population-based study. Lancet 368:1005–11 [Google Scholar]
  110. Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS. 110.  1999. Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N. Engl. J. Med. 341:142–47 [Google Scholar]
  111. Rossebo AB, Pedersen TR, Boman K, Brudi P, Chambers JB. 111.  et al. 2008. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N. Engl. J. Med. 359:1343–56 [Google Scholar]
  112. Owens DS, Otto CM. 112.  2009. Is it time for a new paradigm in calcific aortic valve disease?. JACC Cardiovasc. Imaging 2:928–30 [Google Scholar]
  113. Mohler ER 3rd, Gannon F, Reynolds C, Zimmerman R, Keane MG, Kaplan FS. 113.  2001. Bone formation and inflammation in cardiac valves. Circulation 103:1522–28 [Google Scholar]
  114. Rajamannan NM, Subramaniam M, Rickard D, Stock SR, Donovan J. 114.  et al. 2003. Human aortic valve calcification is associated with an osteoblast phenotype. Circulation 107:2181–84 [Google Scholar]
  115. Visconti RP, Ebihara Y, LaRue AC, Fleming PA, McQuinn TC. 115.  et al. 2006. An in vivo analysis of hematopoietic stem cell potential: hematopoietic origin of cardiac valve interstitial cells. Circ. Res. 98:690–96 [Google Scholar]
  116. Deb A, Wang SH, Skelding K, Miller D, Simper D, Caplice N. 116.  2005. Bone marrow-derived myofibro-blasts are present in adult human heart valves. J. Heart Valve Dis. 14:674–78 [Google Scholar]
  117. Gössl M, Khosla S, Zhang X, Higano N, Jordan KL. 117.  et al. 2012. Role of circulating osteogenic progenitor cells in calcific aortic stenosis. J. Am. Coll. Cardiol. 60:1945–53 [Google Scholar]
  118. Yip CY, Chen JH, Zhao R, Simmons CA. 118.  2009. Calcification by valve interstitial cells is regulated by the stiffness of the extracellular matrix. Arterioscler. Thromb. Vasc. Biol. 29:936–42 [Google Scholar]
  119. Miller JD, Chu Y, Brooks RM, Richenbacher WE, Peña-Silva R, Heistad DD. 119.  2008. Dysregulation of antioxidant mechanisms contributes to increased oxidative stress in calcific aortic valvular stenosis in humans. J. Am. Coll. Cardiol. 52:843–50 [Google Scholar]
  120. Richards J, El-Hamamsy I, Chen S, Sarang Z, Sarathchandra P. 120.  et al. 2013. Side-specific endothelial-dependent regulation of aortic valve calcification: interplay of hemodynamics and nitric oxide signaling. Am. J. Pathol. 182:1922–31 [Google Scholar]
  121. Kennedy JA, Hua X, Mishra K, Murphy GA, Rosenkranz AC, Horowitz JD. 121.  2009. Inhibition of calcifying nodule formation in cultured porcine aortic valve cells by nitric oxide donors. Eur. J. Pharmacol. 602:28–35 [Google Scholar]
  122. Farrar EJ, Huntley GD, Butcher J. 122.  2015. Endothelial-derived oxidative stress drives myofibroblastic activation and calcification of the aortic valve. PLOS ONE 10:e0123257 [Google Scholar]
  123. El Accaoui RN, Gould ST, Hajj GP, Chu Y, Davis MK. 123.  et al. 2014. Aortic valve sclerosis in mice deficient in endothelial nitric oxide synthase. Am. J. Physiol. Heart Circ. Physiol. 306:H1302–13 [Google Scholar]
  124. Roberts WC, Ko JM. 124.  2005. Frequency by decades of unicuspid, bicuspid, and tricuspid aortic valves in adults having isolated aortic valve replacement for aortic stenosis, with or without associated aortic regurgitation. Circulation 111:920–25 [Google Scholar]
  125. Roberts WC, Ko JM, Hamilton C. 125.  2005. Comparison of valve structure, valve weight, and severity of the valve obstruction in 1849 patients having isolated aortic valve replacement for aortic valve stenosis (with or without associated aortic regurgitation) studied at 3 different medical centers in 2 different time periods. Circulation 112:3919–29 [Google Scholar]
  126. Pierpont ME, Basson CT, Benson DW Jr., Gelb BD, Giglia TM. 126.  et al. 2007. Genetic basis for congenital heart defects: current knowledge. A scientific statement from the American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young. Circulation 115:3015–38 [Google Scholar]
  127. Wirrig EE, Yutzey KE. 127.  2014. Conserved transcriptional regulatory mechanisms in aortic valve development and disease. Arterioscler. Thromb. Vasc. Biol. 34:737–41 [Google Scholar]
  128. Chandra S, Rajamannan NM, Sucosky P. 128.  2012. Computational assessment of bicuspid aortic valve wall-shear stress: implications for calcific aortic valve disease. Biomech. Model. Mechanobiol. 11:1085–96 [Google Scholar]
  129. Bonachea EM, Zender G, White P, Corsmeier D, Newsom D. 129.  et al. 2014. Use of a targeted, combinatorial next-generation sequencing approach for the study of bicuspid aortic valve. BMC Med. Genom. 7:56 [Google Scholar]
  130. Prakash SK, Bosse Y, Muehlschlegel JD, Michelena HI, Limongelli G. 130.  et al. 2014. A roadmap to investigate the genetic basis of bicuspid aortic valve and its complications: insights from the International BAVCon (Bicuspid Aortic Valve Consortium). J. Am. Coll. Cardiol. 64:832–39 [Google Scholar]
  131. Lee B, Godfrey M, Vitale E, Hori H, Mattei MG. 131.  et al. 1991. Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature 352:330–34 [Google Scholar]
  132. Dietz HC, Cutting GR, Pyeritz RE, Maslen CL, Sakai LY. 132.  et al. 1991. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature 352:337–39 [Google Scholar]
  133. Ewart AK, Morris CA, Atkinson D, Jin W, Sternes K. 133.  et al. 1993. Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Nat. Genet. 5:11–16 [Google Scholar]
  134. Curran ME, Atkinson DL, Ewart AK, Morris CA, Leppert MF, Keating MT. 134.  1993. The elastin gene is disrupted by a translocation associated with supravalvular aortic stenosis. Cell 73:159–68 [Google Scholar]
  135. Starman BJ, Eyre D, Charbonneau H, Harrylock M, Weis MA. 135.  et al. 1989. Osteogenesis imperfecta. The position of substitution for glycine by cysteine in the triple helical domain of the pro alpha 1(I) chains of type I collagen determines the clinical phenotype. J. Clin. Investig. 84:1206–14 [Google Scholar]
  136. Foffa I, Ait Alì L, Panesi P, Mariani M, Festa P. 136.  et al. 2013. Sequencing of NOTCH1, GATA5, TGFBR1 and TGFBR2 genes in familial cases of bicuspid aortic valve. BMC Med. Genet. 14:44 [Google Scholar]
  137. Theodoris CV, Li M, White MP, Liu L, He D. 137.  et al. 2015. Human disease modeling reveals integrated transcriptional and epigenetic mechanisms of NOTCH1 haploinsufficiency. Cell 160:1072–86 [Google Scholar]
  138. Li DY, Toland AE, Boak BB, Atkinson DL, Ensing GJ. 138.  et al. 1997. Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis. Hum. Mol. Genet. 6:1021–28 [Google Scholar]
  139. Superti-Furga A, Gugler E, Gitzelmann R, Steinmann B. 139.  1988. Ehlers-Danlos syndrome type IV: a multi-exon deletion in one of the two COL3A1 alleles affecting structure, stability, and processing of type III procollagen. J. Biol. Chem. 263:6226–32 [Google Scholar]
  140. Guo DC, Pannu H, Tran-Fadulu V, Papke CL, Yu RK. 140.  et al. 2007. Mutations in smooth muscle α-actin (ACTA2) lead to thoracic aortic aneurysms and dissections. Nat. Genet. 39:1488–93 [Google Scholar]
  141. Pannu H, Tran-Fadulu V, Papke CL, Scherer S, Liu Y. 141.  et al. 2007. MYH11 mutations result in a distinct vascular pathology driven by insulin-like growth factor 1 and angiotensin II. Hum. Mol. Genet. 16:2453–62 [Google Scholar]
  142. Kyndt F, Gueffet JP, Probst V, Jaafar P, Legendre A. 142.  et al. 2007. Mutations in the gene encoding filamin A as a cause for familial cardiac valvular dystrophy. Circulation 115:40–49 [Google Scholar]
  143. Bonachea EM, Chang SW, Zender G, LaHaye S, Fitzgerald-Butt S. 143.  et al. 2014. Rare GATA5 sequence variants identified in individuals with bicuspid aortic valve. Pediatr. Res. 76:211–16 [Google Scholar]
  144. Qu XK, Qiu XB, Yuan F, Wang J, Zhao CM. 144.  et al. 2014. A novel NKX2.5 loss-of-function mutation associated with congenital bicuspid aortic valve. Am. J. Cardiol. 114:1891–95 [Google Scholar]
  145. Dargis N, Lamontagne M, Gaudreault N, Sbarra L, Henry C. 145.  et al. 2016. Identification of gender-specific genetic variants in patients with bicuspid aortic valve. Am. J. Cardiol. 117:420–26 [Google Scholar]
  146. Attias D, Stheneur C, Roy C, Collod-Béroud G, Detaint D. 146.  et al. 2009. Comparison of clinical presentations and outcomes between patients with TGFBR2 and FBN1 mutations in Marfan syndrome and related disorders. Circulation 120:2541–49 [Google Scholar]
  147. Wooten EC, Iyer LK, Montefusco MC, Hedgepeth AK, Payne DD. 147.  et al. 2010. Application of gene network analysis techniques identifies AXIN1/PDIA2 and endoglin haplotypes associated with bicuspid aortic valve. PLOS ONE 5:e8830 [Google Scholar]
  148. Martin LJ, Pilipenko V, Kaufman KM, Cripe L, Kottyan LC. 148.  et al. 2014. Whole exome sequencing for familial bicuspid aortic valve identifies putative variants. Circ. Cardiovasc. Genet. 7:677–83 [Google Scholar]
  149. Laforest B, Andelfinger G, Nemer M. 149.  2011. Loss of Gata5 in mice leads to bicuspid aortic valve. J. Clin. Investig. 121:2876–87 [Google Scholar]
  150. Biben C, Weber R, Kesteven S, Stanley E, McDonald L. 150.  et al. 2000. Cardiac septal and valvular dysmorphogenesis in mice heterozygous for mutations in the homeobox gene Nkx2-5. Circ. Res. 87:888–95 [Google Scholar]
  151. Lee TC, Zhao YD, Courtman DW, Stewart DJ. 151.  2000. Abnormal aortic valve development in mice lacking endothelial nitric oxide synthase. Circulation 101:2345–48 [Google Scholar]
  152. Lewandowski SL, Janardhan HP, Trivedi CM. 152.  2015. Histone deacetylase 3 coordinates deacetylase-independent epigenetic silencing of transforming growth factor-β1 (TGF-β1) to orchestrate second heart field development. J. Biol. Chem. 290:27067–89 [Google Scholar]
  153. Akerberg BN, Sarangam ML, Stankunas K. 153.  2015. Endocardial Brg1 disruption illustrates the developmental origins of semilunar valve disease. Dev. Biol. 407:158–72 [Google Scholar]
  154. Mommersteeg MT, Yeh ML, Parnavelas JG, Andrews WD. 154.  2015. Disrupted Slit-Robo signalling results in membranous ventricular septum defects and bicuspid aortic valves. Cardiovasc. Res. 106:55–66 [Google Scholar]
  155. Quintero-Rivera F, Xi QJ, Keppler-Noreuil KM, Lee JH, Higgins AW. 155.  et al. 2015. MATR3 disruption in human and mouse associated with bicuspid aortic valve, aortic coarctation and patent ductus arteriosus. Hum. Mol. Genet. 24:2375–89 [Google Scholar]
  156. Dupuis LE, Osinska H, Weinstein MB, Hinton RB, Kern CB. 156.  2013. Insufficient versican cleavage and Smad2 phosphorylation results in bicuspid aortic and pulmonary valves. J. Mol. Cell. Cardiol. 60:50–59 [Google Scholar]
  157. Thomas PS, Sridurongrit S, Ruiz-Lozano P, Kaartinen V. 157.  2012. Deficient signaling via Alk2 (Acvr1) leads to bicuspid aortic valve development. PLOS ONE 7:e35539 [Google Scholar]
  158. Leung C, Liu Y, Lu X, Kim M, Drysdale TA, Feng Q. 158.  2016. Rac1 signaling is required for anterior second heart field cellular organization and cardiac outflow tract development. J. Am. Heart Assoc. 5:e002508 [Google Scholar]
  159. Kern CB, Wessels A, McGarity J, Dixon LJ, Alston E. 159.  et al. 2010. Reduced versican cleavage due to Adamts9 haploinsufficiency is associated with cardiac and aortic anomalies. Matrix Biol 29:304–16 [Google Scholar]
  160. Hanada K, Vermeij M, Garinis GA, de Waard MC, Kunen MG. 160.  et al. 2007. Perturbations of vascular homeostasis and aortic valve abnormalities in fibulin-4 deficient mice. Circ. Res. 100:738–46 [Google Scholar]
  161. Snider P, Hinton RB, Moreno-Rodriguez RA, Wang J, Rogers R. 161.  et al. 2008. Periostin is required for maturation and extracellular matrix stabilization of noncardiomyocyte lineages of the heart. Circ. Res. 102:752–60 [Google Scholar]
  162. MacGrogan D, D'Amato G, Travisano S, Martinez-Poveda B, Luxán G. 162.  et al. 2016. Sequential ligand-dependent Notch signaling activation regulates valve primordium formation and morphogenesis. Circ. Res. 118:1480–97 [Google Scholar]
  163. Park EJ, Ogden LA, Talbot A, Evans S, Cai CL. 163.  et al. 2006. Required, tissue-specific roles for Fgf8 in outflow tract formation and remodeling. Development 133:2419–33 [Google Scholar]
  164. Chang CP, Stankunas K, Shang C, Kao SC, Twu KY, Cleary ML. 164.  2008. Pbx1 functions in distinct regulatory networks to pattern the great arteries and cardiac outflow tract. Development 135:3577–86 [Google Scholar]
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Developmental Mechanisms of Aortic Valve Malformation and Disease
Annual Review of Physiology 79, 21 (2017); https://doi.org/10.1146/annurev-physiol-022516-034001
/content/journals/10.1146/annurev-physiol-022516-034001
/content/journals/10.1146/annurev-physiol-022516-034001
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