Skip to main content
SpringerLink
Log in
Book cover

Cardiac Fibrosis and Heart Failure: Cause or Effect? pp 109–123Cite as

Embryological Origin of Valve Progenitor Cells

  • Chapter
  • First Online:

  • 1298 Accesses

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 13))

Abstract

The cardiac valves are required for unidirectional blood flow, preventing backflow during diastole. The adult mammalian heart includes four valves: the aortic, pulmonary, mitral and tricuspid valves. Cardiac valves all have common features, notably a stratified structure consisting of three layers of specialized interstitial cells and extracellular matrix. However, the “semilunar” aortic and pulmonary valves and “atrioventricular” tricuspid and mitral valves have notably different embryonic origins. Indeed, several cell lineages, including endocardium, epicardium and neural crest, are valvulogenic. The endocardium, or inner endothelial lining of the heart, makes major contributions to all valves by undergoing endothelial-to-mesenchymal transition. Neural crest and epicardium make secondary contributions to the semilunar and atrioventricular valves, respectively.

The embryonic origins of endocardium, and valve progenitors within, are still not entirely elucidated. The current paradigm stipulates that endocardium is mainly derived from two early embryonic fields, the first and second heart fields. Further delineating the origins of valve progenitors and their specification towards the valve lineages is essential for understanding cardiac congenital defects. Furthermore, it will be essential for developing therapeutic strategies ranging from pharmacological interventions to improving valve replacement. Finally, the biology of valve progenitors is highly relevant to cardiac fibrosis. Indeed, endothelial to mesenchymal transition of endothelium, comparable to that generating valve mesenchyme, is considered to be a major contributor to cardiac fibrosis. However, it has recently been shown that a more likely source of most, if not all, EndoMT derived fibroblasts in heart is EndoMT associated with valvulogenesis.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M (2006) Burden of valvular heart diseases: a population-based study. Lancet 368:1005–1011

    Article  PubMed  Google Scholar 

  2. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Soliman EZ, Sorlie PD, Sotoodehnia N, Turan TN, Virani SS, Wong ND, Woo D, Turner MB (2012) Heart disease and stroke statistics–2012 update: a report from the American Heart Association. Circulation 125:e2–e220

    Article  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. Combs MD, Yutzey KE (2009) Heart valve development: regulatory networks in development and disease. Circ Res 105:408–421

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Buckingham M, Meilhac S, Zaffran S (2005) Building the mammalian heart from two sources of myocardial cells. Nat Rev Genet 6:826–835

    Article  CAS  PubMed  Google Scholar 

  6. Cai CL, Liang X, Shi Y, Chu PH, Pfaff SL, Chen J, Evans S (2003) Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Dev Cell 5:877–889

    Article  CAS  PubMed  Google Scholar 

  7. de Vlaming A, Sauls K, Hajdu Z, Visconti RP, Mehesz AN, Levine RA, Slaugenhaupt SA, Hagege A, Chester AH, Markwald RR, Norris RA (2012) Atrioventricular valve development: new perspectives on an old theme. Differentiation 84:103–116

    Article  PubMed Central  PubMed  Google Scholar 

  8. Pucéat M (2012) Embryological origin of the endocardium and derived valve progenitor cells: from developmental biology to stem cell-based valve repair. Biochim Biophys Acta 1833(4):917–922

    Google Scholar 

  9. Milgrom-Hoffman M, Harrelson Z, Ferrara N, Zelzer E, Evans SM, Tzahor E (2011) The heart endocardium is derived from vascular endothelial progenitors. Development (Cambridge, England) 138:4777–4787

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Blin G, Nury D, Stefanovic S, Neri T, Guillevic O, Brinon B, Bellamy V, Rucker-Martin C, Barbry P, Bel A, Bruneval P, Cowan C, Pouly J, Mitalipov S, Gouadon E, Binder P, Hagege A, Desnos M, Renaud JF, Menasche P, Puceat M (2010) A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates. J Clin Invest 120:1125–1139

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Neri T, Van Vliet P, Hiriart E, Norris R, Faure E, Zaffran S, Faustino R, Sugi Y, Levine R, De la Pompa J, Terzic A, Evans S, Markwald R (2014) Human embryonic stem cells recapitulate early cardiac valvulogenesis (submitted)

    Google Scholar 

  12. Christoffels VM, Habets PE, Franco D, Campione M, de Jong F, Lamers WH, Bao ZZ, Palmer S, Biben C, Harvey RP, Moorman AF (2000) Chamber formation and morphogenesis in the developing mammalian heart. Dev Biol 223:266–278

    Article  CAS  PubMed  Google Scholar 

  13. Stankunas K, Hang CT, Tsun ZY, Chen H, Lee NV, Wu JI, Shang C, Bayle JH, Shou W, Iruela-Arispe ML, Chang CP (2008) Endocardial Brg1 represses ADAMTS1 to maintain the microenvironment for myocardial morphogenesis. Dev Cell 14(2):298–311

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Moorman AF, Christoffels VM (2003) Cardiac chamber formation: development, genes, and evolution. Physiol Rev 83:1223–1267

    Article  CAS  PubMed  Google Scholar 

  15. Simoes-Costa MS, Vasconcelos M, Sampaio AC, Cravo RM, Linhares VL, Hochgreb T, Yan CY, Davidson B, Xavier-Neto J (2005) The evolutionary origin of cardiac chambers. Dev Biol 277:1–15

    Article  CAS  PubMed  Google Scholar 

  16. Sugi Y, Markwald RR (1996) Formation and early morphogenesis of endocardial endothelial precursor cells and the role of endoderm. Dev Biol 175:66–83

    Article  CAS  PubMed  Google Scholar 

  17. Cohen-Gould L, Mikawa T (1996) The fate diversity of mesodermal cells within the heart field during chicken early embryogenesis. Dev Biol 177:265–273

    Article  CAS  PubMed  Google Scholar 

  18. Lee RK, Stainier DY, Weinstein BM, Fishman MC (1994) Cardiovascular development in the zebrafish. II. Endocardial progenitors are sequestered within the heart field. Development 120(12):3361–3366

    CAS  PubMed  Google Scholar 

  19. Linask KK, Lash JW (1993) Early heart development: dynamics of endocardial cell sorting suggests a common origin with cardiomyocytes. Dev Dyn (an official publication of the American Association of Anatomists) 196:62–69

    Article  CAS  Google Scholar 

  20. Misfeldt AM, Boyle SC, Tompkins KL, Bautch VL, Labosky PA, Baldwin HS (2009) Endocardial cells are a distinct endothelial lineage derived from Flk1+ multipotent cardiovascular progenitors. Dev Biol 333:78–89

    Article  CAS  PubMed  Google Scholar 

  21. Ema M, Takahashi S, Rossant J (2006) Deletion of the selection cassette, but not cis-acting elements, in targeted Flk1-lacZ allele reveals Flk1 expression in multipotent mesodermal progenitors. Blood 107:111–117

    Article  CAS  PubMed  Google Scholar 

  22. Stanley EG, Biben C, Elefanty A, Barnett L, Koentgen F, Robb L, Harvey RP (2002) Efficient Cre-mediated deletion in cardiac progenitor cells conferred by a 3ʹUTR-ires-Cre allele of the homeobox gene Nkx2-5. Int J Dev Biol 46:431–439

    CAS  PubMed  Google Scholar 

  23. Ferdous A, Caprioli A, Iacovino M, Martin CM, Morris J, Richardson JA, Latif S, Hammer RE, Harvey RP, Olson EN, Kyba M, Garry DJ (2009) Nkx2-5 transactivates the Ets-related protein 71 gene and specifies an endothelial/endocardial fate in the developing embryo. Proc Natl Acad Sci U S A 106:814–819

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Kattman SJ, Huber TL, Keller GM (2006) Multipotent flk-1+ cardiovascular progenitor cells give rise to the cardiomyocyte, endothelial, and vascular smooth muscle lineages. Dev Cell 11:723–732

    Article  CAS  PubMed  Google Scholar 

  25. Moretti A, Caron L, Nakano A, Lam JT, Bernshausen A, Chen Y, Qyang Y, Bu L, Sasaki M, Martin-Puig S, Sun Y, Evans SM, Laugwitz KL, Chien KR (2006) Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell 127:1151–1165

    Article  CAS  PubMed  Google Scholar 

  26. Stainier DY, Weinstein BM, Detrich HW, 3rd, Zon LI, Fishman MC (1995) Cloche, an early acting zebrafish gene, is required by both the endothelial and hematopoietic lineages. Development 121:3141–3150

    CAS  PubMed  Google Scholar 

  27. Meilhac SM, Esner M, Kelly RG, Nicolas JF, Buckingham ME (2004) The clonal origin of myocardial cells in different regions of the embryonic mouse heart. Dev Cell 6:685–698

    Article  CAS  PubMed  Google Scholar 

  28. Meilhac SM, Kelly RG, Rocancourt D, Eloy-Trinquet S, Nicolas JF, Buckingham ME (2003) A retrospective clonal analysis of the myocardium reveals two phases of clonal growth in the developing mouse heart. Development 130:3877–3889

    Article  CAS  PubMed  Google Scholar 

  29. Mikawa T, Fischman DA (1992) Retroviral analysis of cardiac morphogenesis: discontinuous formation of coronary vessels. Proc Natl Acad Sci U S A 89:9504–9508

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Mikawa T, Gourdie RG (1996) Pericardial mesoderm generates a population of coronary smooth muscle cells migrating into the heart along with ingrowth of the epicardial organ. Dev Biol 174:221–232

    Article  CAS  PubMed  Google Scholar 

  31. Gittenberger-de Groot AC, Vrancken Peeters MP, Mentink MM, Gourdie RG, Poelmann RE (1998) Epicardium-derived cells contribute a novel population to the myocardial wall and the atrioventricular cushions. Circ Res 82:1043–1052

    Article  CAS  PubMed  Google Scholar 

  32. Wessels A, van den Hoff MJ, Adamo RF, Phelps AL, Lockhart MM, Sauls K, Briggs LE, Norris RA, van Wijk B, Perez-Pomares JM, Dettman RW, Burch JB (2012) Epicardially derived fibroblasts preferentially contribute to the parietal leaflets of the atrioventricular valves in the murine heart. Dev Biol 366:111–124

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Le Douarin NM, Dupin E (2012) The neural crest in vertebrate evolution. Curr Opin Genet Dev 22:381–389

    Article  PubMed  Google Scholar 

  34. Kirby ML, Gale TF, Stewart DE (1983) Neural crest cells contribute to normal aorticopulmonary septation. Science (New York, NY) 220:1059–1061

    Article  CAS  PubMed  Google Scholar 

  35. Waldo K, Miyagawa-Tomita S, Kumiski D, Kirby ML (1998) Cardiac neural crest cells provide new insight into septation of the cardiac outflow tract: aortic sac to ventricular septal closure. Dev Biol 196:129–144

    Article  CAS  PubMed  Google Scholar 

  36. Jiang X, Rowitch DH, Soriano P, McMahon AP, Sucov HM (2000) Fate of the mammalian cardiac neural crest. Development 127:1607–1616

    CAS  PubMed  Google Scholar 

  37. Hinton RB Jr, Lincoln J, Deutsch GH, Osinska H, Manning PB, Benson DW, Yutzey KE (2006) Extracellular matrix remodeling and organization in developing and diseased aortic valves. Circ Res 98:1431–1438

    Article  CAS  PubMed  Google Scholar 

  38. Chin C, Gandour-Edwards R, Oltjen S, Choy M (1992) Fate of the atrioventricular endocardial cushions in the developing chick heart. Pediatr Res 32:390–393

    Article  CAS  PubMed  Google Scholar 

  39. de Lange FJ, Moorman AF, Anderson RH, Manner J, Soufan AT, de Gier-de Vries C, Schneider MD, Webb S, van den Hoff MJ, Christoffels VM (2004) Lineage and morphogenetic analysis of the cardiac valves. Circ Res 95:645–654

    Article  PubMed  Google Scholar 

  40. Hay ED (1995) An overview of epithelio-mesenchymal transformation. Acta Anat 154:8–20

    Article  CAS  PubMed  Google Scholar 

  41. Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Invest 119:1420–1428

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Eisenberg LM, Markwald RR (1995) Molecular regulation of atrioventricular valvuloseptal morphogenesis. Circ Res 77:1–6

    Article  CAS  PubMed  Google Scholar 

  43. Timmerman LA, Grego-Bessa J, Raya A, Bertran E, Perez-Pomares JM, Diez J, Aranda S, Palomo S, McCormick F, Izpisua-Belmonte JC, de la Pompa JL (2004) Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev 18:99–115

    Google Scholar 

  44. Butcher JT, Markwald RR (2007) Valvulogenesis: the moving target. Philos Trans R Soc Lond B Biol Sci 362:1489–1503

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  46. Sprague HB, Mallory TB, Chapman EM (1947) (Calcific aortic stenosis). N Engl J Med 237:958–960

    Article  CAS  PubMed  Google Scholar 

  47. Wylie-Sears J, Aikawa E, Levine RA, Yang JH, Bischoff J (2011) Mitral valve endothelial cells with osteogenic differentiation potential. Arterioscler Thromb Vasc Biol 31:598–607

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Paranya G, Vineberg S, Dvorin E, Kaushal S, Roth SJ, Rabkin E, Schoen FJ, Bischoff J (2001) Aortic valve endothelial cells undergo transforming growth factor-beta-mediated and non-transforming growth factor-beta-mediated transdifferentiation in vitro. Am J Pathol 159:1335–1343

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Liu AC, Joag VR, Gotlieb AI (2007) The emerging role of valve interstitial cell phenotypes in regulating heart valve pathobiology. Am J Pathol 171:1407–1418

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Galante A, Pietroiusti A, Vellini M, Piccolo P, Possati G, De Bonis M, Grillo RL, Fontana C, Favalli C (2001) C-reactive protein is increased in patients with degenerative aortic valvular stenosis. J Am Coll Cardiol 38:1078–1082

    Article  CAS  PubMed  Google Scholar 

  51. Khosla S, Eghbali-Fatourechi GZ (2006) Circulating cells with osteogenic potential. Ann N Y Acad Sci 1068:489–497

    Article  CAS  PubMed  Google Scholar 

  52. Gossl M, Khosla S, Zhang X, Higano N, Jordan KL, Loeffler D, Enriquez-Sarano M, Lennon RJ, McGregor U, Lerman LO, Lerman A (2012) Role of circulating osteogenic progenitor cells in calcific aortic stenosis. J Am Coll Cardiol 60:1945–1953

    Article  PubMed Central  PubMed  Google Scholar 

  53. Sun L, Rajamannan NM, Sucosky P (2013) Defining the role of fluid shear stress in the expression of early signaling markers for calcific aortic valve disease. PloS One 8:e84433

    Article  PubMed Central  PubMed  Google Scholar 

  54. Jian B, Narula N, Li QY, Mohler ER 3rd, Levy RJ (2003) Progression of aortic valve stenosis: TGF-beta1 is present in calcified aortic valve cusps and promotes aortic valve interstitial cell calcification via apoptosis. Ann Thorac Surg 75:457–465; discussion 465–456

    Article  PubMed  Google Scholar 

  55. Kaden JJ, Dempfle CE, Grobholz R, Tran HT, Kilic R, Sarikoc A, Brueckmann M, Vahl C, Hagl S, Haase KK, Borggrefe M (2003) Interleukin-1 beta promotes matrix metalloproteinase expression and cell proliferation in calcific aortic valve stenosis. Atherosclerosis 170:205–211

    Article  CAS  PubMed  Google Scholar 

  56. Walker GA, Masters KS, Shah DN, Anseth KS, Leinwand LA (2004) Valvular myofibroblast activation by transforming growth factor-beta: implications for pathological extracellular matrix remodeling in heart valve disease. Circ Res 95:253–260

    Article  CAS  PubMed  Google Scholar 

  57. Cushing MC, Mariner PD, Liao JT, Sims EA, Anseth KS (2008) Fibroblast growth factor represses Smad-mediated myofibroblast activation in aortic valvular interstitial cells. FASEB J 22:1769–1777

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Gould ST, Matherly EE, Smith JN, Heistad DD, Anseth KS (2014) The role of valvular endothelial cell paracrine signaling and matrix elasticity on valvular interstitial cell activation. Biomaterials 35:3596–3606

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Yip CY, Chen JH, Zhao R, Simmons CA (2009) Calcification by valve interstitial cells is regulated by the stiffness of the extracellular matrix. Arterioscler Thromb Vasc Biol 29:936–942

    Article  CAS  PubMed  Google Scholar 

  60. Caira FC, Stock SR, Gleason TG, McGee EC, Huang J, Bonow RO, Spelsberg TC, McCarthy PM, Rahimtoola SH, Rajamannan NM (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 47:1707–1712

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Miller JD, Weiss RM, Serrano KM, Castaneda LE, Brooks RM, Zimmerman K, Heistad DD (2010) Evidence for active regulation of pro-osteogenic signaling in advanced aortic valve disease. Arterioscler Thromb Vasc Biol 30:2482–2486

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Kaden JJ, Bickelhaupt S, Grobholz R, Haase KK, Sarikoc A, Kilic R, Brueckmann M, Lang S, Zahn I, Vahl C, Hagl S, Dempfle CE, Borggrefe M (2004) Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulate aortic valve calcification. J Mol Cell Cardiol 36:57–66

    Article  CAS  PubMed  Google Scholar 

  63. Garg V, Muth AN, Ransom JF, Schluterman MK, Barnes R, King IN, Grossfeld PD, Srivastava D (2005) Mutations in NOTCH1 cause aortic valve disease. Nature 437(7056):270–274

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. INSERM UMR_S910, Team physiopathology of cardiac development, Medical School La Timone, Aix-Marseille University, 27 Bd Jean Moulin, 13885, Marseille, Cedex 05, France

    Dr. Michel Pucéat & Thomas Moore-Morris

Authors
  1. Dr. Michel Pucéat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Moore-Morris
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michel Pucéat .

Editor information

Editors and Affiliations

  1. Institute of Cardiovascular Sciences St. Boniface Hospital Research Centre Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Canada

    Ian M.C. Dixon

  2. Institute of Cardiovascular Sciences St. Boniface Hospital Research Centre Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada

    Jeffrey T. Wigle

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Pucéat, M., Moore-Morris, T. (2015). Embryological Origin of Valve Progenitor Cells. In: Dixon, I., Wigle, J. (eds) Cardiac Fibrosis and Heart Failure: Cause or Effect?. Advances in Biochemistry in Health and Disease, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-319-17437-2_7

Download citation

Publish with us

Policies and ethics

Search

Navigation