Skip to main content

Advertisement

Log in

Endothelial cell lineages of the heart

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

During early gastrulation, vertebrate embryos begin to produce endothelial cells (ECs) from the mesoderm. ECs first form primitive vascular plexus de novo and later differentiate into arterial, venous, capillary, and lymphatic ECs. In the heart, the five distinct EC types (endocardial, coronary arterial, venous, capillary, and lymphatic) have distinct phenotypes. For example, coronary ECs establish a typical vessel network throughout the myocardium, whereas endocardial ECs form a large epithelial sheet with no angiogenic sprouting into the myocardium. Neither coronary arteries, veins, and capillaries, nor lymphatic vessels fuse with the endocardium or open to the heart chamber. The developmental stage during which the specific phenotype of each cardiac EC type is determined remains unclear. The mechanisms involved in EC commitment and diversity can however be more precisely defined by tracking the migratory patterns and lineage decisions of the precursors of cardiac ECs.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Antin PB, Yatskievych T, Dominguez JL, Chieffi P (1996) Regulation of avian precardiac mesoderm development by insulin and insulin-like growth factors. J Cell Physiol 168:42–50

    Article  PubMed  CAS  Google Scholar 

  • Anversa P, Nadal-Ginard B (2002) Myocyte renewal and ventricular remodelling. Nature 415:240–243

    Article  PubMed  CAS  Google Scholar 

  • Bayes-Genis A, Muniz-Diaz E, Catasus L, Arilla M, Rodriguez C, Sierra J, Madoz PJ, Cinca J (2004) Cardiac chimerism in recipients of peripheral-blood and bone marrow stem cells. Eur J Heart Fail 6:399–402

    Article  PubMed  Google Scholar 

  • Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbanek K, Leri A, Kajstura J, Nadal-Ginard B, Anversa P (2003) Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114:763–776

    Article  PubMed  CAS  Google Scholar 

  • Bernanke DH, Velkey JM (2002) Development of the coronary blood supply: changing concepts and current ideas. Anat Rec 269:198–208

    Article  PubMed  Google Scholar 

  • Bogers AJ, Gittenberger-de Groot AC, Poelmann RE, Péault BM, Huysmans HA (1989) Development of the origin of the coronary arteries, a matter of ingrowth or outgrowth? Anat Embryol (Berl) 180:437–441

    Article  CAS  Google Scholar 

  • Cai CL, Martin JC, Sun Y, Cui L, Wang L, Ouyang K, Yang L, Bu L, Liang X, Zhang X, Stallcup WB, Denton CP, McCulloch A, Chen J, Evans SM (2008) A myocardial lineage derives from Tbx18 epicardial cells. Nature doi: 10.1038/nature06969

  • Coffin JD, Poole TJ (1988) Embryonic vascular development: immunohistochemical identification of the origin and subsequent morphogenesis of the major vessel primordia in quail embryos. Development 102:735–748

    PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Conte G, Pellegrini A (1984) On the development of the coronary arteries in human embryos, stages 14–19. Anat Embryol 169:209–218

    Article  PubMed  CAS  Google Scholar 

  • Dettman RW, Denetclaw W Jr, Ordahl CP, Bristow J (1998) Common epicardial origin of coronary vascular smooth muscle, perivascular fibroblasts, and intermyocardial fibroblasts in the avian heart. Dev Biol 193:169–181

    Article  PubMed  CAS  Google Scholar 

  • Duncan SA (2003) Mechanisms controlling early development of the liver. Mech Dev 120:19–33

    Article  PubMed  CAS  Google Scholar 

  • Eisenberg CA, Bader D (1995) QCE-6: a clonal cell line with cardiac myogenic and endothelial cell potentials. Dev Biol 167:469–481

    Article  PubMed  CAS  Google Scholar 

  • Flamme I, Risau W (1992) Induction of vasculogenesis and hematopoiesis in vitro. Development 116:435–439

    PubMed  CAS  Google Scholar 

  • Folkman J, Klagsbrun M (1987) Angiogenic factors. Science 235:442–447

    Article  PubMed  CAS  Google Scholar 

  • Fukuda-Taira S (1981) Hepatic induction in the avian embryo: specificity of reactive endoderm and inductive mesoderm. J Embryol Exp Morph 63:111–125

    PubMed  CAS  Google Scholar 

  • Garcia-Martinez V, Schoenwolf GC (1993) Primitive-streak origin of the cardiovascular system in avian embryos. Dev Biol 159:706–719

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Gualdi R, Bossard P, Zheng M, Hamada Y, Coleman JR, Zaret KS (1996) Hepatic specification of the gut endoderm in vitro: cell signaling and transcriptional control. Genes Dev 10:1670–1682

    Article  PubMed  CAS  Google Scholar 

  • Hatcher CJ, Diman NY, Kim MS, Pennisi D, Song Y, Goldstein MM, Mikawa T, Basson CT (2004) A role for Tbx5 in proepicardial cell migration during cardiogenesis. Physiol Genomics 18:129–140

    Article  PubMed  CAS  Google Scholar 

  • Hirakow R (1983) Development of the cardiac blood vessels in staged human embryos. Acta Anat 115:220–230

    Article  PubMed  CAS  Google Scholar 

  • Hiruma T, Hirakow R (1989) Epicardial formation in embryonic chick heart: computer-aided reconstruction, scanning, and transmission electron microscopic studies. Am J Anat 184:129–138

    Article  PubMed  CAS  Google Scholar 

  • His W (1868) Untersuchungen über die erste Anlage des Wirbeltierleibes. Vogel, Leipzig

    Google Scholar 

  • His W (1900) Lecithoblast und Angioblast der Wirbeltiere, Abh Math-Phys Kl Ges 26:171–328

    Google Scholar 

  • Ho E, Shimada Y (1978) Formation of the epicardium studied with the scanning electron microscope. Dev Biol 66:579–585

    Article  PubMed  CAS  Google Scholar 

  • Hutchins GM, Kessler-Hanna A, Moore GW (1988) Development of the coronary arteries in the embryonic human heart. Circulation 77:1250–1257

    PubMed  CAS  Google Scholar 

  • Ishii Y, Langberg JD, Hurtado R, Lee S, Mikawa T (2007) Induction of proepicardial marker gene expression by the liver primordium. Development 134:3627–3637

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Kajstura J, Rota M, Whang B, Cascapera S, Hosoda T, Bearzi C, Nurzynska D, Kasahara H, Zias E, Bonafé M, Nadal-Ginard B, Torella D, Nascimbene A, Quaini F, Urbanek K, Leri A, Anversa P (2005) Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. Circ Res 96:127–137

    Article  PubMed  CAS  Google Scholar 

  • Kirschhoffer K von, Grim M, Christ B, Wachtler F (1994) Emergence of myogenic and endothelial cell lineages in avian embryos. Dev Biol 163:270–278

    Article  Google Scholar 

  • Kruithof BP, Wijk B van, Somi S, Kruithof-de Julio M, Pérez Pomares JM, Weesie F, Wessels A, Moorman AF, Hoff MJ van den (2006) BMP and FGF regulate the differentiation of multipotential pericardial mesoderm into the myocardial or epicardial lineage. Dev Biol 295:507–522

    Article  PubMed  CAS  Google Scholar 

  • Landerholm TE, Dong XR, Lu J, Belaguli NS, Schwartz RJ, Majesky MW (1999) A role for serum response factor in coronary smooth muscle differentiation from proepicardial cells. Development 126:2053–2062

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Leri A, Kajstura J, Anversa P (2005) Cardiac stem cells and mechanisms of myocardial regeneration. Physiol Rev 85:1373–1416

    Article  PubMed  CAS  Google Scholar 

  • Linask KK, Lash JW (1993) Early heart development: dynamics of endocardial cell sorting suggests a common origin with cardiomyocytes. Dev Dyn 196:62–69

    PubMed  CAS  Google Scholar 

  • Lough J, Barron M, Brogley M, Sugi Y, Bolender DL, Zhu X (1996) Combined BMP-2 and FGF-4, but neither factor alone, induces cardiogenesis in non-precardiac embryonic mesoderm. Dev Biol 178:198–202

    Article  PubMed  CAS  Google Scholar 

  • Majesky MW (2004) Development of coronary vessels. Curr Top Dev Biol 62:225–259

    Article  PubMed  CAS  Google Scholar 

  • Männer J (1992)The development of pericardial villi in the chick embryo. Anat Embryol (Berl) 186:379–385

    Google Scholar 

  • Männer J (1999) Does the subepicardial mesenchyme contribute myocardioblasts to the myocardium of the chick embryo heart? A quail-chick chimera study tracing the fate of the epicardial primordium? Anat Rec 255:212–226

    Article  PubMed  Google Scholar 

  • Männer J (2006) Extracardiac tissues and the epigenetic control of myocardial development in vertebrate embryos. Ann Anat 188:199–212

    Article  PubMed  CAS  Google Scholar 

  • Männer J, Perez-Pomares JM, Macias D, Munoz-Chapuli R (2001) The origin, formation and developmental significance of the epicardium: a review. Cells Tissues Organs 169:89–103

    Article  PubMed  Google Scholar 

  • Matsuura K, Nagai T, Nishigaki N, Oyama T, Nishi J, Wada H, Sano M, Toko H, Akazawa H, Sato T, Nakaya H, Kasanuki H, Komuro I (2004) Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. J Biol Chem 279:11384–11391

    Article  PubMed  CAS  Google Scholar 

  • Messina E, De Angelis L, Frati G, Morrone S, Chimenti S, Fiordaliso F, Salio M, Battaglia M, Latronico MV, Coletta M, Vivarelli E, Frati L, Cossu G, Giacomello A (2004) Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res 95:911–921

    Article  PubMed  CAS  Google Scholar 

  • Mikawa T (1998) Cardiac lineages. In: Harvey RP, Rosenthal N (eds) Heart development, Academic Press, New York, pp 19–33

    Google Scholar 

  • Mikawa T, Fischman DA (1992) Retroviral analysis of cardiac morphogenesis: discontinuous formation of coronary vessels. Proc Nat Acad Sci USA 89:9504–9508

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Mikawa T, Cohen-Gould L, Fischman DA (1992) Clonal analysis of cardiac morphogenesis in the chicken embryo using a replication-defective retrovirus. III. Polyclonal origin of adjacent ventricular myocytes. Dev Dyn 195:133–141

    PubMed  CAS  Google Scholar 

  • Mohri T, Fujio Y, Maeda M, Ito T, Iwakura T, Oshima Y, Uozumi Y, Segawa M, Yamamoto H, Kishimoto T, Azuma J (2006) Leukemia inhibitory factor induces endothelial differentiation in cardiac stem cells. J Biol Chem 281:6442–6447

    Article  PubMed  CAS  Google Scholar 

  • Moorman AF, Christoffels VM, Anderson RH, Hoff MJ van den (2007) The heart-forming fields: one or multiple? Philos Trans R Soc Lond Biol 362:1257–1265

    Article  PubMed  Google Scholar 

  • Nahirney PC, Mikawa T, Fischman DA (2003) Evidence for an extracellular matrix bridge guiding proepicardial cell migration to the myocardium of chick embryos. Dev Dyn 227:511–523

    Article  PubMed  Google Scholar 

  • Oh H, Bradfute SB, Gallardo TD, Nakamura T, Gaussin V, Mishina Y, Pocius J, Michael LH, Behringer RR, Garry DJ, Entman ML, Schneider MD (2003) Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci USA 100:12313–12318

    Article  PubMed  CAS  Google Scholar 

  • Olivey HE, Mundell NA, Austin AF, Barnett JV (2006) Transforming growth factor-beta stimulates epithelial-mesenchymal transformation in the proepicardium. Dev Dyn 235:50–59

    Article  PubMed  CAS  Google Scholar 

  • Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705

    Article  PubMed  CAS  Google Scholar 

  • Pardanaud L, Dieterlen-Lievre F (1999) Manipulation of the angiogenic/hemangiopoietic commitment in the avian embryo. Development 126:617–627

    PubMed  CAS  Google Scholar 

  • Quaini F, Urbanek K, Beltrami AP, Finato N, Beltrami CA, Nadal-Ginard B, Kajstura J, Leri A, Anversa P (2002) Chimerism of the transplanted heart. N Engl J Med 346:5–15

    Article  PubMed  Google Scholar 

  • Rawles ME (1943) The heart forming regions of the chick blastoderm. Physiol Zool 16:22–42

    Google Scholar 

  • Reagan FP (1915) Vascularization phenomena in fragments of embryonic bodies completely isolated from yolk sac endoderm. Anat Rec 9:329–341

    Article  Google Scholar 

  • Redkar A, Montgomery M, Litvin J (2002) Fate map of early avian cardiac progenitor cells. Development 128:2269–2279

    Google Scholar 

  • Reese DE, Zavaljevski M, Streiff NL, Bader D (1999) bves: A novel gene expressed during coronary blood vessel development. Dev Biol 209:159–171

    Article  PubMed  CAS  Google Scholar 

  • Reese DE, Mikawa T, Bader DM (2002) Development of the coronary vessel system. Circ Res 91:761–768

    Article  PubMed  CAS  Google Scholar 

  • Robb L, Mifsud L, Hartley L, Biben C, Copeland NG, Gilbert DJ, Jenkins NA, Harvey RP (1998) epicardin: A novel basic helix-loop-helix transcription factor gene expressed in epicardium, branchial arch myoblasts, and mesenchyme of developing lung, gut, kidney, and gonads. Dev Dyn 213:105–113

    Article  PubMed  CAS  Google Scholar 

  • Rosenquist RL, DeHaan GC (1966) Migration of precardiac cells in the chick embryo: a radioautographic study. Carnegie Inst Washington Contrib Embryol 625:111–121

    Google Scholar 

  • Rychter Z, Ostádal B (1971a) Fate of “sinusoidal” intertrabecular spaces of the cardiac wall after development of the coronary vascular bed in chick embryo. Folia Morphol (Praha) 19:31-44

    CAS  Google Scholar 

  • Rychter Z, Ostádal B (1971b) Mechanism of the development of coronary arteries in chick embryo. Folia Morphol (Praha) 19:113-124

    CAS  Google Scholar 

  • Sabin FR (1909) The lymphatic system in human embryos, with a consideration of the system as a whole. Am J Anat 9:43–91

    Article  Google Scholar 

  • Sater AK, Jacobson AG (1989) The specification of heart mesoderm occurs during gastrulation in Xenopus laevis. Development 105:821–830

    PubMed  CAS  Google Scholar 

  • Schlueter J, Männer J, Brand T (2006) BMP is an important regulator of proepicardial identity in the chick embryo. Dev Biol 295:546–558

    Article  PubMed  CAS  Google Scholar 

  • Schneider M, Othman-Hassan K, Christ B, Wilting J (1999) Lymphangioblasts in the avian wing bud. Dev Dyn 216:311–319

    Article  PubMed  CAS  Google Scholar 

  • Schultheiss TM, Lassar AB (1997) Induction of chick cardiac myogenesis by bone morphogenetic proteins. Cold Spring Harb Symp Quant Biol 62:413–419

    PubMed  CAS  Google Scholar 

  • Schultheiss TM, Xydas S, Lassar AB (1995) Induction of avian cardiac myogenesis by anterior endoderm. Development 121:4203–4214

    PubMed  CAS  Google Scholar 

  • Schultheiss T, Burch J, Lassar A (1997) A role for bone morphogenetic proteins in the induction of cardiac myogenesis. Genes Dev 11:451–462

    Article  PubMed  CAS  Google Scholar 

  • Silva GV, Litovsky S, Assad JA, Sousa AL, Martin BJ, Vela D, Coulter SC, Lin J, Ober J, Vaughn WK, Branco RV, Oliveira EM, He R, Geng YJ, Willerson JT, Perin EC (2005) Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 111:150–156

    Article  PubMed  CAS  Google Scholar 

  • Stalsberg H, DeHaan RL (1969) The precardiac areas and formation of the tubular heart in the chick embryo. Dev Biol 19:128–159

    Article  PubMed  CAS  Google Scholar 

  • Thiele J, Varus E, Wickenhauser C, Kvasnicka HM, Lorenzen J, Gramley F, Metz KA, Rivero F, Beelen DW (2004) Mixed chimerism of cardiomyocytes and vessels after allogeneic bone marrow and stem-cell transplantation in comparison with cardiac allografts. Transplantation 77:1902–1905

    Article  PubMed  Google Scholar 

  • Tomanek RJ (2005) Formation of the coronary vasculature during development. Angiogenesis 8:273–284

    Article  PubMed  Google Scholar 

  • Tomanek RJ, Ishii Y, Holifield JS, Sjogren CL, Hansen HK, Mikawa T (2006) VEGF family members regulate myocardial tubulogenesis and coronary artery formation in the embryo. Circ Res 98:947–953

    Article  PubMed  CAS  Google Scholar 

  • Torella D, Ellison GM, Karakikes I, Nadal-Ginard B (2007) Resident cardiac stem cells. Cell Mol Life Sci 64:661–673

    Article  PubMed  CAS  Google Scholar 

  • Viragh S, Challice CE (1981) The origin of the epicardium and the embryonic myocardial circulation in the mouse. Anat Rec 201:157–168

    Article  PubMed  CAS  Google Scholar 

  • Viragh S, Gittenberger-de Groot AC, Poelmann RE, Kalman F (1993) Early development of quail heart epicardium and associated vascular and glandular structures. Anat Embryol (Berl) 188:381–393

    CAS  Google Scholar 

  • Vrancken Peeters MP, Gittenberger-de Groot AC, Mentink MM, Poelmann RE (1999) Smooth muscle cells and fibroblasts of the coronary arteries derive from epithelial-mesenchymal transformation of the epicardium. Anat Embryol (Berl) 199:367–378

    Article  CAS  Google Scholar 

  • Watt AJ, Battle MA, Li J, Duncan SA (2004) GATA4 is essential for formation of the proepicardium and regulates cardiogenesis. Proc Natl Acad Sci USA 101:12573–12578

    Article  PubMed  CAS  Google Scholar 

  • Wei Y, Mikawa T (2000) Fate diversity of primitive streak cells during heart field formation in ovo. Dev Dyn 219:505–513

    Article  PubMed  CAS  Google Scholar 

  • Wessels A, Perez-Pomares JM (2004) The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells. Anat Rec 276A:43–57

    Article  Google Scholar 

  • Wilting J, Buttler K, Schulte I, Papoutsi M, Schweigerer L, Männer J (2007) The proepicardium delivers hemangioblasts but not lymphangioblasts to the developing heart. Dev Biol 305:451–459

    Article  PubMed  CAS  Google Scholar 

  • Yatskievych TA, Ladd AN, Antin PB (1997) Induction of cardiac myogenesis in avian pregastrula epiblast: the role of the hypoblast and activin. Development 124:2561–2570

    PubMed  CAS  Google Scholar 

Download references

Acknowledgement

We thank Ms. Alicia Navetta for her comments on the manuscript, and Ms. Sharrell B. Lee for her assistance with cell culture.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Takashi Mikawa.

Additional information

Work carried out by the authors is supported in part by the NIH.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ishii, Y., Langberg, J., Rosborough, K. et al. Endothelial cell lineages of the heart. Cell Tissue Res 335, 67–73 (2009). https://doi.org/10.1007/s00441-008-0663-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-008-0663-z

Keywords

Navigation