The atrioventricular valves are the pulmonary and aortic valves

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What are heart valves?

The heart consists of four chambers, two atria (upper chambers) and two ventricles (lower chambers). There is a valve through which blood passes before leaving each chamber of the heart. The valves prevent the backward flow of blood. These valves are actual flaps that are located on each end of the two ventricles (lower chambers of the heart). They act as one-way inlets of blood on one side of a ventricle and one-way outlets of blood on the other side of a ventricle. Normal valves have three flaps, except the mitral valve, which has two flaps. The four heart valves include the following:

  • tricuspid valve: located between the right atrium and the right ventricle
  • pulmonary valve: located between the right ventricle and the pulmonary artery
  • mitral valve: located between the left atrium and the left ventricle
  • aortic valve: located between the left ventricle and the aorta

How do the heart valves function?

As the heart muscle contracts and relaxes, the valves open and shut, letting blood flow into the ventricles and atria at alternate times. The following is a step-by-step illustration of how the valves function normally in the left ventricle:

After the left ventricle contracts, the aortic valve closes and the mitral valve opens, to allow blood to flow from the left atrium into the left ventricle.

As the left atrium contracts, more blood flows into the left ventricle.

When the left ventricle contracts, the mitral valve closes and the aortic valve opens, so blood flows into the aorta.

What is heart valve disease?

Heart valves can have one of two malfunctions:

  1. regurgitation (or leakage of the valve): The valve(s) does not close completely, causing the blood to flow backward through the valve. This results in leakage of blood back back into the atria from the ventricles (in the case of the mitral and tricuspid valves) or leakage of blood back into the ventricles (in the case of the aortic and pulmonary valves).
  2. stenosis (or narrowing of the valve): The valve(s) opening becomes narrowed or valves become damaged or scarred (stiff), inhibiting the flow of blood out of the ventricles or atria. The heart is forced to pump blood with increased force in order to move blood through the narrowed or stiff (stenotic) valve(s).

Heart valves can have both malfunctions at the same time (regurgitation and stenosis). Also, more than one heart valve can be affected at the same time. When heart valves fail to open and close properly, the implications for the heart can be serious, possibly hampering the heart's ability to pump blood adequately through the body. Heart valve problems are one cause of heart failure.

1. Schoen FJ. Evolving concepts of cardiac valve dynamics. Circulation. 2008;118:1864–1880. [PubMed] [Google Scholar]

2. Armstrong EJ, Bischoff J. Heart valve development: Endothelial cell signaling and differentiation. Circ Res. 2004;95:459–470. [PMC free article] [PubMed] [Google Scholar]

3. Bruneau BG. The developmental genetics of congenital heart disease. Nature. 2008;451:943–948. [PubMed] [Google Scholar]

4. Sacks MS, David Merryman W, Schmidt DE. On the biomechanics of heart valve function. J Biomech. 2009;42:1804–1824. [PMC free article] [PubMed] [Google Scholar]

5. Hoffman JIE, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol. 2002;39:1890–1900. [PubMed] [Google Scholar]

6. Bonow RO, Carabello BA, Kanu C, de Leon AC, Jr, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O’Gara PT, O’Rourke RA, Otto CM, Shah PM, Shanewise JS, Smith SC, Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Lytle BW, Nishimura R, Page RL, Riegel B. ACC/AHA 2006 guidelines 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 (writing committee to revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. Circulation. 2006;114:e84–e231. [PubMed] [Google Scholar]

7. Supino PG, Borer JS, Preibisz J, Bornstein A. The epidemiology of valvular heart disease: a growing public health problem. Heart Fail Clin. 2006;2:379–393. [PubMed] [Google Scholar]

8. Roberts WC, Ko JM. 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. 2005;2005:920–925. [PubMed] [Google Scholar]

9. Anderson RH, Ho SY, Becker AE. Anatomy of the human atrioventricular junctions revisited. Anat Rec. 2000;260:81–91. [PubMed] [Google Scholar]

11. Misfeld M, Sievers HH. Heart valve macro- and microstructure. Philos Trans R Soc Lond B Biol Sci. 2007;362:1421–1436. [PMC free article] [PubMed] [Google Scholar]

12. Lincoln J, Lange AW, Yutzey KE. Hearts and bones: Shared regulatory mechanisms in heart valve, cartilage, tendon, and bone development. Dev Biol. 2006;294:292–302. [PubMed] [Google Scholar]

13. Zimmerman J, MBailey C. The surgical significance of the fibrous skeleton of the heart. J Thorac Cardiovasc Surg. 1962;44:701–712. [Google Scholar]

14. Yacoub MH, Kilner PJ, Birks EJ, Misfeld M. The aortic outflow and root: a tale of dynamism and crosstalk. Ann Thorac Surg. 1999;68:S37–S43. [PubMed] [Google Scholar]

15. Choo SJ, McRae G, Olomon JP, St George G, Davis W, Burleson-Bowles CL, Pang D, Luo HH, Vavra D, Cheung DT, Oury JH, Duran CM. Aortic root geometry: pattern of differences between leaflets and sinuses of Valsalva. J Heart Valve Dis. 1999;8:407–415. [PubMed] [Google Scholar]

16. Otto CM, Kuusisto J, Reichenbach DD, Gown AM, O’Brien KD. Characterization of the early lesion of ‘degenerative’ valvular aortic stenosis. Histological and immunohistochemical studies. Circulation. 1994;90:844–853. [PubMed] [Google Scholar]

17. Rabkin E, Aikawa M, Stone JR, Fukumoto Y, Libby P, Schoen FJ. Activated interstitial myofibroblasts express catabolic enzymes and mediate matrix remodeling in myxomatous heart valves. Circulation. 2001;104:2525–2532. [PubMed] [Google Scholar]

18. Combs MD, Yutzey KE. Heart valve development: Regulatory networks in development and disease. Circ Res. 2009;105:408–421. [PMC free article] [PubMed] [Google Scholar]

19. Person AD, Klewer SE, Runyan RB. Cell biology of cardiac cushion development. Int Rev Cytol. 2005;243:287–335. [PubMed] [Google Scholar]

20. de Lange FJ, Moorman AFM, Anderson RH, Manner J, Soufan AT, deGier-deVries C, Schneider MD, Webb S, Van Den Hoff MJ, Christoffels VM. Lineage and morphogenetic analysis of the cardiac valves. Circ Res. 2004;95:645–654. [PubMed] [Google Scholar]

21. Lincoln J, Alfieri CM, Yutzey KE. Development of heart valve leaflets and supporting apparatus in chicken and mouse embryos. Dev Dyn. 2004;230:239–250. [PubMed] [Google Scholar]

22. Schroeder JA, Jackson LF, Lee DC, Camenisch TD. Form and function of developing heart valves: coordination by extracellular matrix growth and signaling. J Mol Med. 2003;81:392–403. [PubMed] [Google Scholar]

23. Butcher JT, McQuinn TC, Sedmera D, Turner D, Markwald RR. Transitions in early embryonic atrioventricular valvular functions correspond with changes in cushion biomechanics that are predictable with tissue composition. Circ Res. 2007;100:1503–1511. [PubMed] [Google Scholar]

24. Hinton RB, Lincoln J, Deutsch GH, Osinska H, Manning PB, Benson DW, Yutzey KE. Extracellular matrix remodeling and organization in developing and diseased aortic valves. Circ Res. 2006;98:1431–1438. [PubMed] [Google Scholar]

25. Aikawa E, Whittaker P, Farber M, Mendelson K, Padera RF, Aikawa M, Schoen FJ. Human semilunar cardiac valve remodeling by activated cells from fetus to adult. Circulation. 2006;113:1344–1352. [PubMed] [Google Scholar]

26. Verzi MP, McCulley DJ, De Val S, Dodou E, Black BL. The right ventricle, outflow tract, and ventricular septum comprise a restricted expression domain within the secondary/anterior heart field. Dev Biol. 2005;287:134–145. [PubMed] [Google Scholar]

27. Snarr BS, Kern CB, Wessels A. Origin and fate of cardiac mesenchyme. Dev Dyn. 2008;237:2804–2819. [PubMed] [Google Scholar]

28. Zhou B, von Gise A, Ma Q, Hu YW, Pu WT. Genetic fate mapping demonstrates contribution of epicardium-derived cells to the annulus fibrosis of the mammalian heart. Dev Biol. 338:251–261. [PMC free article] [PubMed] [Google Scholar]

29. Gittenberger-de Groot AC, Peeters MPFMV, Mentink MMT, Gourdie RG, Poelmann RE. Epicardium-derived cells contribute a novel population to the myocardial wall and the atrioventricular cushions. Circ Res. 1998;82:1043–1052. [PubMed] [Google Scholar]

30. Nakamura T, Colbert MC, Robbins J. Neural crest cells retain multipotential characteristics in the developing valves and label the cardiac conduction system. Circ Res. 2006;98:1547–1554. [PubMed] [Google Scholar]

31. Ma L, Lu MF, Schwartz RJ, Martin JF. Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning. Development. 2005;132:5601–5611. [PubMed] [Google Scholar]

32. Hurlstone AF, Haramis AP, Wienholds E, Begthel H, Korving J, Van Eeden F, Zivkovic D, Plasterk RH, Clevers H. The Wnt/beta-catenin pathway regulates cardiac valve formation. Nature. 2003;425:633–537. [PubMed] [Google Scholar]

33. Liebner S, Cattelino A, Gallini R, Rudini N, Iurlaro M, Piccolo S, Dejana E. Beta-catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse. J Cell Biol. 2004;166:359–367. [PMC free article] [PubMed] [Google Scholar]

34. Timmerman LA, Grego-Bessa J, Raya A, Bertran E, Perez-Pomares JM, Diez J, Aranda S, Palomo S, McCormick F, Izpisua-Belmonte JC, delaPompa JL. Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev. 2004;18:99–115. [PMC free article] [PubMed] [Google Scholar]

35. Yang JH, Weinberg RA. Epithelial-Mesenchymal transition: At the crossroads of development and tumor metastasis. Dev Cell. 2008;14:818–829. [PubMed] [Google Scholar]

36. Shelton EL, Yutzey KE. Twist1 function in endocardial cell proliferation, migration, and differentiation during heart valve development. Dev Biol. 2008;317:282–295. [PMC free article] [PubMed] [Google Scholar]

37. Chakraborty S, Cheek J, Sakthivel B, Aronow BJ, Yutzey KE. Shared gene expression profiles in developing heart valves and osteoblasts. Physiol Genomics. 2008;35:75–85. [PMC free article] [PubMed] [Google Scholar]

38. de la Pompa JL, Timmerman LA, Takimoto H, Yoshida H, Elia AJ, Samper E, Potter J, Wakeham A, Marengere L, Langille BL, Crabtree GR, Mak TW. Role of NF-ATc transcription factor in morphogenesis of cardiac valves and septum. Nature. 1998;392:182–186. [PubMed] [Google Scholar]

39. Ranger AM, Grusby MJ, Gravallese EM, de la Brousse FC, Hoey T, Mickanin C, Baldwin HS, Glimcher LH. The transcription factor NF-ATc is essential for cardiac valve formation. Nature. 1998;392:186–190. [PubMed] [Google Scholar]

40. Combs MD, Yutzey KE. VEGF and RANKL regulation of NFATc1 in heart valve development. Circ Res. 2008;105:565–574. [PMC free article] [PubMed] [Google Scholar]

41. Lincoln J, Alfieri CM, Yutzey KE. BMP and FGF regulatory pathways control cell lineage diversification of heart valve precursor cells. Dev Biol. 2006;292:290–302. [PubMed] [Google Scholar]

42. Zhao B, Etter L, Hinton RB, Benson DW. BMP and FGF regulatory pathways in semilunar valve precursor cells. Dev Dyn. 2007;236:971–980. [PubMed] [Google Scholar]

43. Alfieri CM, Cheek J, Chakraborty S, Yutzey KE. Wnt signaling in heart valve development and osteogenic gene induction. Dev Biol. 2010;338:127–135. [PMC free article] [PubMed] [Google Scholar]

44. Kruithof BPT, Krawitz SA, Gaussin V. Atrioventricular valve development during late embryonic and postnatal stages involves condensation and extracellular matrix remodeling. Dev Biol. 2007;302:208–217. [PubMed] [Google Scholar]

45. Gross L, Kugel MA. Topographic anatomy and histology of the valves in the human heart. Am J Path. 1931;7:445–456. [PMC free article] [PubMed] [Google Scholar]

46. Broom ND. The observation of collagen and elastin structures in wet whole mounts of pulmonary and aortic leaflets. J Thorac Cardiovasc Surg. 1978;75:121–130. [PubMed] [Google Scholar]

47. Missirlis YF, Armeniades CD. Ultrastructure of the human aortic valve. Acta Anat (Basel) 1977;98:199–205. [PubMed] [Google Scholar]

48. Kershaw JD, Misfeld M, Sievers HH, Yacoub MH, Chester AH. Specific regional and directional contractile responses of aortic cusp tissue. J Heart Valve Dis. 2004;13:798–803. [PubMed] [Google Scholar]

49. Sacks MS, Yoganathan AP. Heart valve function: a biomechanical perspective. Philos Trans R Soc Lond B Biol Sci. 2007;362:1369–1391. [PMC free article] [PubMed] [Google Scholar]

50. Schoen FJ. Aortic valve structure-function correlations: Role of elastic fibers no longer a stretch of the imagination. J Heart Valve Dis. 1997;6:1–6. [PubMed] [Google Scholar]

51. Vesely I. The role of elastin in aortic valve mechanics. J Biomech. 1998;31:115–123. [PubMed] [Google Scholar]

52. Camenisch TD, Spicer AP, Brehm-Gibson T, Biesterfeldt J, Augustine ML, Calabro AJ, Kubalak S, Klewer SE, McDonald JA. Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme. J Clin Invest. 2000;106:349–360. [PMC free article] [PubMed] [Google Scholar]

53. Mjaatvedt CH, Yamamura H, Capehart AA, Turner D, Markwald RR. The cspg2 gene, disrupted in the hdf mutant, is required for right cardiac chamber and endocardial cushion formation. Dev Biol. 1998;202:56–66. [PubMed] [Google Scholar]

54. Costell M, Carmona R, Gustafsson E, Gonzalez-Iriarte M, Fassler R, Munoz-Chapuli R. Hyperplastic conotruncal endocardial cushions and transposition of great arteries in perlecan-null mice. Circ Res. 2002;91:158–164. [PubMed] [Google Scholar]

55. Wirrig EE, Snarr BS, Chintalapudi MR, O’Neal JL, Phelps AL, Barth JL, Fresco VM, Kern CB, Mjaatvedt CH, Toole BP, Hoffman S, Trusk TC, Argraves WS, Wessels A. Cartilage link protein 1 (Crtl1), an extracellular matrix component playing an important role in heart development. Dev Biol. 2007;310:291–303. [PMC free article] [PubMed] [Google Scholar]

56. Li DY, Brooke B, Davis EC, Mecham RP, Sorensen LK, Boak BB, Eichwald E, Keating MT. Elastin is an essential determinant of arterial morphogenesis. Nature. 1998;393:276–280. [PubMed] [Google Scholar]

57. Li DY, Faury G, Taylor DG, Davis EC, Boyle WA, Mecham RPPS, Boak B, Keating MT. Novel arterial pathology in mice and humans hemizygous for elastin. J Clin Invest. 1998;102:1783–1787. [PMC free article] [PubMed] [Google Scholar]

58. Hinton RB, Adelman-Brown J, Witt S, Krishnamurthy VK, Osinska H, Sakthivel B, James JF, Narmoneva DA, Mecham RP, Benson DW. Elastin Haploinsufficiency results in progressive aortic valve malformation and latent valve disease in a mouse model. Circ Res. 2010 In press. [PMC free article] [PubMed] [Google Scholar]

59. Snider P, Hinton RB, Moreno-Rodriguez R, Wang J, Rogers R, Lindsley A, Li F, Ingram DA, Menick D, Field L, Firulli AB, Molkentin JD, Markwald RR, Conway SJ. Periostin is required for maturation and extracellular matrix stabilization of noncardiomyocyte lineages of the heart. Circ Res. 2008;102:752–760. [PMC free article] [PubMed] [Google Scholar]

60. Norris RA, Moreno-Rodriguez R, Sugi Y, Hoffman S, Amos J, Hart MM, Potts JD, Goodwin RL, Markwald RR. Periostin regulates atrioventricular valve maturation. Dev Biol. 2008;316:200–213. [PMC free article] [PubMed] [Google Scholar]

61. Lincoln J, Florer JB, Deutsch GH, Wenstrup RJ, Yutzey KE. ColVa1 and ColXIa1 are required for ventricular chamber morphogenesis and heart valve development. Dev Dyn. 2006;235:3295–3305. [PubMed] [Google Scholar]

62. Otto CM. Valvular aortic stenosis: disease severity and timing of intervention. J Am Coll Cardiol. 2006;47:2141–2151. [PubMed] [Google Scholar]

63. Vesely I, Noseworthy R. Micromechanics of the fibrosa and the ventricularis in aortic valve leaflets. J Biomech. 1992;25:101–113. [PubMed] [Google Scholar]

64. Grande KJ, Cochran RP, Reinhall PG, Kunzelman KS. Stress variations in the human aortic root and valve: the role of anatomic asymmetry. Ann Biomed Eng. 1998;26:534–545. [PubMed] [Google Scholar]

65. Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Stafford R, Thom T, Wasserthiel-Smoller S, Wong ND, Wylie-Rosett J. Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. 121:e46–e215. [PubMed] [Google Scholar]

66. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases: a population-based study. Lancet. 2006;368:1005–1011. [PubMed] [Google Scholar]

67. Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS. Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Engl J Med. 1999;341:142–147. [PubMed] [Google Scholar]

68. Rajamannan NM, Gersh B, Bonow RO. Calcific aortic stenosis: from bench to the bedside--emerging clinical and cellular concepts. Heart. 2003;89:801–805. [PMC free article] [PubMed] [Google Scholar]

69. Pierpont ME, Basson CT, Benson DW, Jr, Gelb BD, Giglia TM, Goldmuntz E, McGee G, Sable CA, Srivastava D, Webb CL. 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: endorsed by the American Academy of Pediatrics. Circulation. 2007;115:3015–3038. [PubMed] [Google Scholar]

70. Garg V, Muth AN, Ransom JF, Schluterman MK, Barnes R, King IN, Grossfeld PD, Srivastava D. Mutations in NOTCH1 cause aortic valve disease. Nature. 2005;437:270–274. [PubMed] [Google Scholar]

71. Martin LJ, Ramachandran V, Cripe LH, Hinton RB, Andelfinger G, Tabangin M, Shooner K, Keddache M, Benson DW. Evidence in favor of linkage to human chromosomal regions 18q, 5q and 13q for bicuspid aortic valve and associated cardiovascular malformations. Hum Genet. 2007;121:275–284. [PubMed] [Google Scholar]

72. Disse S, Abergel E, Berrebi A, Houot AM, Le Heuzey JY, Diebold B, Guize L, Carpentier A, Corvol P, Jeunemaitre X. Mapping of a first locus for autosomal dominant myxomatous mitral-valve prolapse to chromosome 16p11.2-p12.1. Am J Hum Genet. 1999;65:1242–1251. [PMC free article] [PubMed] [Google Scholar]

73. Freed LA, Acierno JSJ, Dai D, Leyne M, Marshall JE, Nesta F, Levine RA, Slaugenhaupt SA. A locus for autosomal dominant mitral valve prolapse on chromosome 11p15.4. Am J Hum Genet. 2003;72:1551–1559. [PMC free article] [PubMed] [Google Scholar]

74. Nesta F, Leyne M, Yosefy C, Simpson C, Dai D, Marshall JE, Hung J, Slaugenhaupt SA, Levine RA. New locus for autosomal dominant mitral valve prolapse on chromosome 13: clinical insights from genetic studies. Circulation. 2005;112:2022–2030. [PubMed] [Google Scholar]

75. Smith DE, Matthews MB. Aortic valvular stenosis with coarctation of the aorta, with special reference to the development of aortic stenosis upon congenital bicuspid valves. Br Heart J. 1955;17:198–206. [PMC free article] [PubMed] [Google Scholar]

76. Roberts WC. The congenitally bicuspid aortic valve. A study of 85 autopsy cases. Am J Cardiol. 1970;26:72–83. [PubMed] [Google Scholar]

77. Pomerance A. Pathogenesis of aortic stenosis and its relation to age. Br Heart J. 1972;34:569–574. [PMC free article] [PubMed] [Google Scholar]

78. Passik CS, Ackermann DM, Pluth JR, Edwards WD. Temporal changes in the causes of aortic stenosis: a surgical pathologic study of 646 cases. Mayo Clin Proc. 1987;62:119–123. [PubMed] [Google Scholar]

79. Peterson MD, Roach RM, Edwards JE. Types of aortic stenosis in surgically removed valves. Arch Pathol Lab Med. 1985;109:829–832. [PubMed] [Google Scholar]

80. Stephan PJ, Henry AC, 3rd, Hebeler RF, Jr, Whiddon L, Roberts WC. Comparison of age, gender, number of aortic valve cusps, concomitant coronary artery bypass grafting, and magnitude of left ventricular-systemic arterial peak systolic gradient in adults having aortic valve replacement for isolated aortic valve stenosis. Am J Cardiol. 1997;79:166–172. [PubMed] [Google Scholar]

81. Bosse Y, Miqdad A, Fournier D, Pepin A, Pibarot P, Mathieu P. Refining molecular pathways leading to calcific aortic valve stenosis by studying gene expression profile of normal and calcified stenotic human aortic valves. Circ Cardiovasc Genet. 2009;2:489–498. [PubMed] [Google Scholar]

82. de Sa M, Moshkovitz Y, Butany J, David TE. Histologic abnormalities of the ascending aorta and pulmonary trunk in patients with bicuspid aortic valve disease: clinical relevance to the ross procedure. J Thorac Cardiovasc Surg. 1999;118:588–594. [PubMed] [Google Scholar]

83. Rossebo AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E, Gohlke-Barwolf C, Holme I, Kesaniemi YA, Malbecq W, Nienaber CA, Ray S, Skjaerpe T, Wachtell K, Willenheimer R. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008;359:1343–1356. [PubMed] [Google Scholar]

84. Rabkin-Aikawa E, Farber M, Aikawa M, Schoen FJ. Dynamic and reversible changes in interstitial cell phenotype during remodeling of cardiac valves. J Heart Valve Disease. 2004;13:841–847. [PubMed] [Google Scholar]

85. Liu AC, Joag VR, Gotlieb AI. The emerging role of valve interstitial cell phenotypes in regulating heart valve pathology. Am J Pathol. 2007;171:1407–1418. [PMC free article] [PubMed] [Google Scholar]

86. Caira FC, Stock SR, Gleason TG, McGee EC, Huang J, Bonow RO, Spelsberg TC, McCarthy PM, Rahimtoola SH, Rajamannan NM. Human degenerative valve disease is associated with up-regulation of low-density lipoprotein-related protein 5 receptor-mediated bone formation. J Am Coll Cardiol. 2006;47:1707–1712. [PMC free article] [PubMed] [Google Scholar]

87. Rajamannan NM, Subramaniam M, Rickard DJ, Stock SR, Donovan J, Springett M, Orszulak T, Fullerton DA, Tajik AJ, Bonow RO, Spelsberg TC. Human aortic valve calcification is associated with an osteoblast phenotype. Circulation. 2003;107:2181–2184. [PMC free article] [PubMed] [Google Scholar]

88. Yip CY, Chen JH, Zhao R, Simmons CA. Calcification by valve interstitial cells is regulated by the stiffness of the extracellular matrix. Arterioscler Thromb Vasc Biol. 2009;29:936–942. [PubMed] [Google Scholar]

89. Filip DA, Radu A, Simionescu M. Interstitial cells of the heart valves posess characteristics similar to smooth muscle cells. Circ Res. 1986;59:310–320. [PubMed] [Google Scholar]

90. Deb A, Wnag SH, Skelding K, Miller D, Simper D, Caplice N. Bone marrow-derived myofibroblasts are present in adult human heart valves. J Heart Valve Dis. 2005;14:674–678. [PubMed] [Google Scholar]

91. Visconti RP, Ebihara Y, LaRue AC, Fleming PA, McQuinn TC, Masuya M, Minamiguchi H, Markwald RR, Ogawa M, Drake CJ. An in vivo analysis of hematopoietic stem cell potential: hematopoietic origin of cardiac valve interstitial cells. Circ Res. 2006;98:690–696. [PubMed] [Google Scholar]

92. Dietz HC, Loeys B, Carta L, Ramirez F. Recent progress towards a molecular understanding of Marfan syndrome. Am J Med Genet. 2005;139C:4–9. [PubMed] [Google Scholar]

93. Ewart AK, Morris CA, Atkinson D, Jin W, Sternes K, Spallone P, Stock AD, Leppert M, Keating MT. Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Nat Genet. 1993;5:11–16. [PubMed] [Google Scholar]

94. Ng CM, Cheng A, Myers LA, Martinez-Murillo F, Jie C, Bedja D, Gabrielson KL, Hausladen JMW, Mecham RP, Judge DP, Dietz HC. TGF-β-dependent pathogenesis of mitral valve prolapse in a mouse model of Marfan syndrome. J Clin Invest. 2004;114:1586–1592. [PMC free article] [PubMed] [Google Scholar]

95. Liu X, Wu H, Byrne M, Krane S, Jaenisch R. Type III collagen is crucial for collagen I fibrillogenesis and for normal cardiovascular development. Proc Nat Acad Sci USA. 1997;94:1852–1856. [PMC free article] [PubMed] [Google Scholar]

96. Starman BJ, Eyre D, Charbonneau H, Harrylock M, Weis MA, Weiss L, Graham JM, Jr, Byers PH. 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 Invest. 1989;84:1206–1214. [PMC free article] [PubMed] [Google Scholar]

97. Weis SM, Emery JL, Becker KD, McBride DJ, Omens JH, McCulloch AD. Myocardial mechanics and collagen structure in the osteogenesis imperfecta murine (oim) Circ Res. 2000;87:663–669. [PubMed] [Google Scholar]

98. Kern CB, Wessels A, McGarity J, Dixon LJ, Alston E, Argraves WS, Geeting D, Nelson CM, Menick DR, Apte SS. Reduced versican cleavage due to Adamts9 haploinsufficiency is associated with cardiac and aortic anomalies. Matrix Biol. 2010;29:304–316. [PMC free article] [PubMed] [Google Scholar]

99. Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys B, Cooper TK, Myers L, Klein EC, Liu G, Calvi C, Podowski M, Neptune ER, Halushka MK, Bedja D, Gabrielson K, Rifkin DB, Carta L, Ramirez F, Huso DL, Dietz HC. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science. 2006;312:117–121. [PMC free article] [PubMed] [Google Scholar]

100. Brooke BS, Habashi JP, Judge DP, Patel N, Loeys B, Dietz HC. Angiotensin II blockade and aortic-root dilation in Marfan’s syndrome. N Engl J Med. 2008;358:2787–2795. [PMC free article] [PubMed] [Google Scholar]

101. Rajamannan NM, Subramaniam M, Caira F, Stock SR, Spelsberg TC. Atorvastatin inhibits hypercholesterolemia-induced calcification in the aortic valves via the Lrp5 receptor pathway. Circulation. 2005;112:I229–I34. [PMC free article] [PubMed] [Google Scholar]

102. Bonhoeffer P, Boudjemline Y, Qureshi SA, Le Bidois J, Iserin L, Acar P, Merckx J, Kachaner J, Sidi D. Percutaneous insertion of the pulmonary valve. J Am Coll Cardiol. 2002;39:1664–1669. [PubMed] [Google Scholar]

103. Vahanian A, Alfieri O, Al-Attar N, Antunes M, Bax J, Cormier B, Cribier A, De Jaegere P, Fournial G, Kappetein AP, Kovac J, Ludgate S, Maisano F, Moat N, Mohr F, Nataf P, Pierard L, Pomar JL, Schofer J, Tornos P, Tuzcu M, van Hout B, Von Segesser LK, Walther T. Transcatheter valve implantation for patients with aortic stenosis: a position statement from the European Association of Cardio-Thoracic Surgery (EACTS) and the European Society of Cardiology (ESC), in collaboration with the European Association of Percutaneous Cardiovascular Interventions (EAPCI) Eur Heart J. 2008;29:1463–1470. [PubMed] [Google Scholar]

104. Costell M, Gustafsson E, Aszodi A, Morgelin M, Bloch W, Hunziker E, Addicks K, Timpl R, Fassler R. Perlecan maintains the integrity of cartilage and some basement membranes. J Cell Biol. 1999;147:1109–1122. [PMC free article] [PubMed] [Google Scholar]

105. Weyman AE, Scherrer-Crosbie M. Marfan syndrome and mitral valve prolapse. J Clin Invest. 2004;114:1543–1546. [PMC free article] [PubMed] [Google Scholar]

106. Hanada K, Vermeij M, Garinis GA, de Waard MC, Kunen MGS, Myers L, Maas A, Duncker DJ, Meijers C, Dietz HC, Kanaar R, Essers J. Perturbations of vascular homeostasis and aortic valve abnormalities in fibulin-4 deficient mice. Circ Res. 2007;100:738–746. [PubMed] [Google Scholar]

107. Kuivaniemi H, Tromp G, Prockop DJ. Mutations in fibrillar collagens (types I, II, III, and XI), fibril-associated collagen (type IX), and network-forming collagen (type X) cause a spectrum of diseases of bone, cartilage, and blood vessels. Hum Mutat. 1997;9:300–315. [PubMed] [Google Scholar]

108. Dietz HC, Cutting GR, Pyeritz RE, Maslen CL, Sakai LY, Corson GM, Puffenberger EG, Hamosh A, Nanthakumar EJ, Curristin SM, Stetten G, Meyers DA, Francomano CA. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1991;352:337–339. [PubMed] [Google Scholar]

109. Li DY, Toland AE, Boak BB, Atkinson DL, Ensing GJ, Morris CA, Keating MT. Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis. Hum Mol Genet. 1997;6:1021–1028. [PubMed] [Google Scholar]

110. Loeys BL, Schwarze U, Holm T, Callewaert BL, Thomas GH, Pannu H, De Backer JF, Oswald GL, Symoens S, Manouvrier S, Roberts AE, Faravelli F, Greco MA, Pyeritz RE, Milewicz DM, Coucke PJ, Cameron DE, Braverman AC, Byers PH, De Paepe AM, Dietz HC. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med. 2006;355:788–798. [PubMed] [Google Scholar]

111. Superti-Furga A, Gugler E, Gitzelmann R, Steinmann B. Ehlers-Danlos syndrome type IV: a muliti-exon deletion in one of the two COL3A1 allels affecting structure, stability, and processing of type III procollagen. J Biol Chem. 1988;263:6226–6232. [PubMed] [Google Scholar]

112. Guo DC, Pannu H, Tran-Fadulu V, Papke CL, Yu RK, Avidan N, Bourgeois S, Estrera AL, Safi HJ, Sparks E, Amor D, Ades L, McConnell V, Willoughby CE, Abuelo D, Willing M, Lewis RA, Kim DH, Scherer S, Tung PP, Ahn C, Buja LM, Raman CS, Shete SS, Milewicz DM. Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections. Nat Genet. 2007;39:1488–1493. [PubMed] [Google Scholar]

113. Pannu H, Tran-Fadulu V, Papke CL, Scherer S, Liu Y, Presley C, Guo D, Estrera AL, Safi HJ, Brasier AR, Vick GW, Marian AJ, Raman CS, Buja LM, Milewicz DM. MYH11 mutations result in a distinct vascular pathology driven by insulin-like growth factor 1 and angiotensin II. Hum Mol Genet. 2007;16:2453–2462. [PMC free article] [PubMed] [Google Scholar]

114. Kyndt F, Gueffet JP, Probst V, Jaafar P, Legendre A, Le Bouffant F, Toquet C, Roy E, McGregor L, Lynch SA, Newbury-Ecob R, Tran V, Young I, Trochu JN, Le Marec H, Schott JJ. Mutations in the gene encoding filamin A as a cause for familial cardiac valvular dystrophy. Circulation. 2007;115:40–49. [PubMed] [Google Scholar]

115. Edwards WD. Cardiac anatomy and examination of cardiac specimens. In: Allen HD, Driscoll DJ, Shaddy RE, Felts TF, editors. Moss and Adams’ heart disease in infants, children, and adolescents. Vol. 1. Philadephia: Lippincott, Williams, and Wilkins; 2008. pp. 2–34. [Google Scholar]

What are the two atrioventricular valves?

The right atrioventricular valve is the tricuspid valve. The left atrioventricular valve is the bicuspid, or mitral, valve. The valve between the right ventricle and pulmonary trunk is the pulmonary semilunar valve.

Is the AV valve The aortic valve?

The mitral and tricuspid atrioventricular (AV) valves separate the atria from the ventricles, while the aortic and pulmonary semilunar (SL) valves separate the ventricles from the great arteries. AV valves have leaflets and SL valves have cusps.

What are atrioventricular valves called?

The atrioventricular valves are the mitral valve, and the tricuspid valve, which are situated between the atria and the ventricles, and prevent backflow from the ventricles into the atria during systole. They are anchored to the walls of the ventricles by chordae tendineae, which prevent them from inverting.

What are the three atrioventricular valves?

The atrioventricular valves, the bicuspid (mitral) and tricuspid valves, separate the atria from the ventricles. The bicuspid valve is on the left side of the heart and the tricuspid valve is on the right side of the heart.