Epicardium as a new target for regenerative technologies in cardiology



Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Epicardium is actively involved in the embryonic heart development and its repair after injury, which allows it to be considered as a potential target for the treatment of heart diseases. In this regard, the study of the mechanisms of its development, the components of the microenvironment, as well as the signals regulating the behavior of epicardial progenitor cells, is the most important area of modern cardiology. This review considers the results of recent studies of homeostasis of epicardial cells and technological advances to modulate their activity, which is essential for the development of new therapeutic agents.

Full Text

Restricted Access

About the authors

K. V Dergilev

Institute of Experimental Cardiology National Medical Research Center for Cardiology

Email: doctorkote@gmail.com
Moscow, Russia

A. V Komova

Institute of Experimental Cardiology National Medical Research Center for Cardiology

Email: doctorkote@gmail.com
Moscow, Russia

Z. I Tsokolaeva

Institute of Experimental Cardiology National Medical Research Center for Cardiology; V.A. Negovsky Research Institute of General Reanimatology Federal Scientific and Clinical Center of Reanimatology and Rehabilitation

Email: doctorkote@gmail.com
Moscow, Russia; Moscow, Russia

I. B Beloglazova

Institute of Experimental Cardiology National Medical Research Center for Cardiology

Email: doctorkote@gmail.com
Moscow, Russia

Ye. V Parfyonova

Institute of Experimental Cardiology National Medical Research Center for Cardiology; M.V. Lomonosov Moscow State University

Email: doctorkote@gmail.com
Moscow, Russia; Moscow, Russia

References

  1. Miao C., Lei M., Hu W., Han S. et al. A brief review: the therapeutic potential of bone marrow mesenchymal stem cells in myocardial infarction. Stem Cell Res. Ther. 2017; 8(1): 242.
  2. Padda J., Sequiera G.L., Sareen N., Dhingra S. Stem cell therapy for cardiac regeneration: hits and misses. Can. J. Physiol. Pharmacol. 2015; 93(10): 835-41.
  3. Bearzi C., Rota M., Hosoda T. et al. Human cardiac stem cells. PNAS USA 2007; 104(35): 14068-14073.
  4. Дергилев К.В., Рубина К.А., Парфенова Е.В. Резидентные стволовые клетки сердца. Кардиология 2011; 51(4): 84-92.
  5. Dergilev K., Tsokolaeva Z., Makarevich P. et al. C-Kit Cardiac Progenitor Cell Based Cell Sheet Improves Vascularization and Attenuates Cardiac Remodeling following Myocardial Infarction in Rats. Biomed. Res. Int. 2018; 2018: 3536854.
  6. Hendrikx M., Fanton Y., Willems L. et al. From Bone Marrow to Cardiac Atrial Appendage Stem Cells for Cardiac Repair: A Review. Curr. Med. Chem. 2016; 23(23): 2421-38.
  7. Дергилев К.В., Рубина К.А., Цоколаева 3.И. и др. Аневризма левого желудочка - возможный источник резидентных стволовых клеток сердца. Цитология 2010; 52(11): 921-30.
  8. van Berlo J.H., Kanisicak O., Maillet M. et al. c-kit+ cells minimally contribute cardiomyocytes to the heart. Nature 2014; 509(7500): 337-41.
  9. Nair N., Gongora E. Stem cell therapy in heart failure: Where do we stand today? Biochim. Biophys. Acta. Mol. Basis Dis. 2019: 165489.
  10. Manasek F.J. Embryonic development of the heart: II. Formation of the epicardium. J. Embryol. Exp. Morphol. 1969; 22(3): 333-48.
  11. Gittenberger-de Groot A.C., Winter E.M., Bartelings M.M. et al. The arterial and cardiac epicardium in development, disease and repair. Differentiation 2012; 84(1): 41-53.
  12. Niderla-BieliNska J., Jankowska-Steifer E., Flaht-Zabost A. et al. Proepicardium: Current Understanding of its Structure, Induction, and Fate. Anat. Rec. 2019; 302(6): 893-903.
  13. Nahirney P.C., Mikawa T., Fischman D.A. Evidence for an extracellular matrix bridge guiding proepicardial cell migration to the myocardium of chick embryos. Dev. Dyn. 2003; 227(4): 511-23.
  14. Kwee L., Baldwin H.S., Shen H.M. et al. Defective development of the embryonic and extraembryonic circulatory systems in vascular cell adhesion molecule (VCAM-1) deficient mice. Dev. 1995; 121(2): 489-503.
  15. Sengbusch J.K., He W., Pinco K.A., Yang J.T. Dual functions of α4β1 integrin in epicardial development: Initial migration and long-term attachment. J. Cell Biol. 2002; 157(5): 873-82.
  16. Pae S.H., Dokic D., Dettman R.W. Communication between integrin receptors facilitates epicardial cell adhesion and matrix organization. Dev. Dyn. 2008; 237(4): 962-78.
  17. Wengerhoff S.M., Weiss A.R., Dwyer K.L., Dettman R.W. A migratory role for EphrinB ligands in avian epicardial mesothelial cells. Dev. Dyn. 2010; 239(2): 598-609.
  18. Hirose T., Karasawa M., Sugitani Y. et al. PAR3 is essential for cyst-mediated epicardial development by establishing apical cortical domains. Dev. 2006; 133(7): 1389-98.
  19. Li J., Miao L., Zhao C. et al. CDC42 is required for epicardial and proepicardial development by mediating FGF receptor trafficking to the plasma membrane. Dev. 2017; 144(9): 1635-647.
  20. Gittenberger-de Groot A.C., Vrancken Peeters M.P.F.M., Bergwerff M. et al. Epicardial outgrowth inhibition leads to compensatory mesothelial outflow tract collar and abnormal cardiac septation and coronary formation. Circ. Res. 2000; 87(11); 969-71.
  21. Perez-Pomares J.M., Carmona R., Gonzalez-Iriarte M. et al. Origin of coronary endothelial cells from epicardial mesothelium in avian embryos. Int. J. Dev. Biol. 2002; 46(8): 1005-13.
  22. Poelmann R.E., Lie-Venema H., Gittenberger-de Groot A.C. The role of the epicardium and neural crest as extracardiac contributors to coronary vascular development. Tex. Heart Inst. J. 2002; 29(4): 255-61.
  23. Rothenberg F., Hitomi M., Fisher S.A., Watanabe M. Initiation of apoptosis in the developing avian outflow tract myocardium. Dev. Dyn. 2002; 223(4): 469-82.
  24. Schaefer K.S., Doughman Y.Q., Fisher S.A., Watanabe M. Dynamic patterns of apoptosis in the developing chicken heart. Dev. Dyn. 2004; 229(3): 489-99.
  25. Lie-Venema H., van den Akker N.M.S., Bax N.A.M. et al. Origin, Fate, and Function of Epicardium-Derived Cells (EPDCs) in Normal and Abnormal Cardiac Development. Scientific World J. 2007; 7: 1777-98.
  26. Pérez-Pomares J.M., Macias D., Garcia-Garrido L., Muñoz-Chápuli R. Contribution of the primitive epicardium to the subepicardial mesenchyme in hamster and chick embryos. Dev. Dyn. 1997; 210(2): 96-105.
  27. Gittenberger-de Groot A.C., Vrancken Peeters M.P.F.M., Bergwerff M. et al. Epicardium-Derived Cells Contribute a Novel Population to the Myocardial Wall and the Atrioventricular Cushions. Circ. Res. 1998; 82(10): 1043-52.
  28. Wu M., Smith C.L., Hall J.A. et al. Epicardial Spindle Orientation Controls Cell Entry into the Myocardium. Dev. Cell. 2010; 19(1): 114-25.
  29. Merki E., Zamora M., Raya A. et al. Epicardial retinoid X receptor a is required for myocardial growth and coronary artery formation. PNAS USA 2005; 102(51): 18455-60.
  30. Smart N., Risebro C.A., Melville A.A. et al. Thymosin ß4 induces adult epicardial progenitor mobilization and neovascularization. Nature 2007; 445(7124): 177-82.
  31. Weeke-Klimp A., Bax N.A.M., Bellu A.R. et al. Epicardium-derived cells enhance proliferation, cellular maturation and alignment of cardiomyocytes. J. Mol. Cell Cardiol. 2010; 49(4): 606-16.
  32. Mellgren A.M., Smith C.L., Olsen G.S. et al. Platelet-derived growth factor receptor ß signaling is required for efficient epicardial cell migration and development of two distinct coronary vascular smooth muscle cell populations. Circ. Res. 2008; 103(12): 1393-401.
  33. Mikawa T., Gourdie R.G. Pericardial Mesoderm Generates a Population of Coronary Smooth Muscle Cells Migrating into the Heart along with Ingrowth of the Epicardial Organ. Dev. Biol. 1996; 174(2): 221-32.
  34. Dettman R.W., Denetclaw Jr.W., Ordahl C.P., Bristowm J. Common Epicardial Origin of Coronary Vascular Smooth Muscle, Perivascular Fibroblasts, and Intermyocardial Fibroblasts in the Avian Heart. Dev. Biol. 1998; 193(2); 169-81.
  35. Männer J. Does the subepicardial mesenchyme contribute myo-cardioblasts to the myocardium of the chick embryo heart? A quail-chick chimera study tracing the fate of the epicardial primordium. Anat. Rec. 1999; 255(2): 212-26.
  36. Cai C.L., Martin J.C., Sun Y.L. et al. A myocardial lineage derives from Tbx18 epicardial cells. Nature 2008; 454(7200): 104-8.
  37. Wessels A., van den Hoff M.J., Adamo R.F. et al. Epicardially derived fibroblasts preferentially contribute to the parietal leaflets of the atrioventricular valves in the murine heart. Dev. Biol. 2012; 366(2): 111-24.
  38. Zhou B., von Gise A., Ma Q. et al. Genetic fate mapping demonstrates contribution of epicardium-derived cells to the annulus fibrosis of the mammalian heart. Dev. Biol. 2010; 338(2): 251-61.
  39. Acharya A., Baek S.T., Huang G. et al. The bHLH transcription factor Tcf21 is required for lineage-specific EMT of cardiac fibroblast progenitors. Dev. 2012; 139(12): 2139-49.
  40. Braitsch C.M., Combs M.D., Quaggin S.E., Yutzey K.E. Pod1/ Tcf21 is regulated by retinoic acid signaling and inhibits differentiation of epicardium-derived cells into smooth muscle in the developing heart. Dev. Biol. 2012; 368(2): 345-57.
  41. Zhou B., Ma Q., Rajagopal S. et al. Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature 2008; 454(7200): 109-13.
  42. Christoffels V.M., Grieskamp T., Norden J. et al. Tbx18 and the fate of epicardial progenitors. Nature 2009; 458(7240): E8-E9.
  43. Red-Horse K., Ueno H., Weissman I.L., Krasnow M.A. Coronary arteries form by developmental reprogramming of venous cells. Nature 2010; 464(7288): 549-53.
  44. Wu B., Zhang Z., Lui W. et al. Endocardial Cells Form the Coronary Arteries by Angiogenesis through Myocardial-Endocardial VEGF Signaling. Cell 2012; 151(5): 1083-96.
  45. Katz T.C., Singh M.K., Degenhardt K. et al. Distinct compartments of the proepicardial organ give rise to coronary vascular endothelial cells. Dev. Cell. 2012; 22(3): 639-50.
  46. Rudat C., Kispert A. Wt1 and epicardial fate mapping. Circ. Res. 2012; 111(2): 165-9.
  47. Olivey H.E., Svensson E.C. Epicardial-myocardial signaling directing coronary vasculogenesis. Circ. Res. 2010; 106(5): 818-32.
  48. Wessels A., Pérez-Pomares J.M. The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells. Anat. Rec. 2004; 276A(1): 43-57.
  49. Lavine K.J., Yu K., White A.C. et al. Endocardial and Epicardial Derived FGF Signals Regulate Myocardial Proliferation and Differentiation In Vivo. Dev. Cell. 2005; 8(1): 85-95.
  50. Lavine K.J., White A.C., Park C. et al. Fibroblast growth factor signals regulate a wave of Hedgehog activation that is essential for coronary vascular development. Genes Dev. 2006; 20(12): 1651-66.
  51. Pennisi D.J., Mikawa T. FGFR-1 is required by epicardium-derived cells for myocardial invasion and correct coronary vascular lineage differentiation. Dev. Biol. 2009; 328(1): 148-59.
  52. Cavallero S., Shen H., Yi C. et al. CXCL12 Signaling Is Essential for Maturation of the Ventricular Coronary Endothelial Plexus and Establishment of Functional Coronary Circulation. Dev. Cell. 2015; 33(4): 469-77.
  53. Lavine K.J., Long F., Choi K. et al. Hedgehog signaling to distinct cell types differentially regulates coronary artery and vein development. Dev. 2008; 135(18): 3161-71.
  54. Chen T.H.P., Chang T.C., Kang J.O. et al. Epicardial Induction of Fetal Cardiomyocyte Proliferation via a Retinoic Acid-Inducible Trophic Factor. Dev. Biol. 2002; 250(1): 198-207.
  55. Zhou B., Honor L.B., He H. et al. Adult mouse epicardium modulates myocardial injury by secreting paracrine factors. J. Clin. Invest. 2011; 121(5): 1894-904.
  56. Limana F., Bertolami C., Mangoni A. et al. Myocardial infarction induces embryonic reprogramming of epicardial c-kit+ cells: Role of the pericardial fluid. J. Mol. Cell Cardiol. 2010; 48(4): 609-18.
  57. Qian L., Huang Y., Spencer C.I. et al. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature 2012; 485(7400): 593-8.
  58. von Gise A., Pu W.T. Endocardial and epicardial epithelial to mesenchymal transitions in heart development and disease. Circ. Res. 2012; 110(12): 1628-45.
  59. Smits A.M, Riley P.R. Epicardium-derived heart repair. Dev. Biol. 2014; 2(2): 84-100.
  60. Lui K., Zangi L, Silva E. et al. Driving vascular endothelial cell fate of human multipotent Isl1 + heart progenitors with VEGF modified mRNA. Cell Res. 2013; 23(10): 1172-86.
  61. Limana F., Zacheo A., Mocini D. et al. Identification of Myocardial and Vascular Precursor Cells in Human and Mouse Epicardium. Circ. Res. 2007; 101(12): 1255-65.
  62. Russell J.L., Goetsch S.C., Gaiano N.R. et al. A dynamic notch injury response activates epicardium and contributes to fibrosis repair. Circ. Res. 2011; 108(1): 51-9.
  63. van Wijk B., Gunst Q.D., Moorman A.F., van den Hoff M.J.B. Cardiac regeneration from activated epicardium. PloS One 2012; 7(9): e44692.
  64. Smart N., Risebro C.A., Clark J.E. et al. Thymosin ß4 facilitates epicardial neovascularization of the injured adult heart. Ann. N.Y. Acad. Sci. 2010; 1194(1): 97-104.
  65. Zangi L., Lui K.O., von Gise A. et al. Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction. Nat. Biotechnol. 2013; 31(10): 898.
  66. Winter E.M., Grauss R.W., Hogers B. et al. Preservation of left ventricular function and attenuation of remodeling after transplantation of human epicardium-derived cells into the infarcted mouse heart. Circ. 2007; 116(8): 917-27.
  67. Limana F., Esposito G., D'Arcangelo D. et al. HMGB1 attenuates cardiac remodelling in the failing heart via enhanced cardiac regeneration and miR-206-mediated inhibition of TIMP-3. PloS One 2011; 6(6): e19845.
  68. Kikuchi K., Holdway J.E., Major R.J. et al. Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration. Dev. Cell. 2011; 20(3): 397-404.
  69. Xiang F.L., Liu Y., Lu X. et al. Cardiac-specific overexpression of human stem cell factor promotes epicardial activation and arteriogenesis after myocardial infarction. Circ. Heart Fail. 2014; 7(5): 831-42.
  70. Urayama K., Guilini C., Turkeri G. et al. Prokineticin receptor-1 induces neovascularization and epicardial-derived progenitor cell differentiation. Arterioscler. Thromb. Vasc. Biol. 2008; 28(5): 841-49.
  71. Smart N., Bollini S., Dube K.N. et al. De novo cardiomyocytes from within the activated adult heart after injury. Nature 2011; 474(7353): 640-4.
  72. Bock-Marquette I., Shrivastava S., Pipes G.T. et al. Thymosin ß4 mediated PKC activation is essential to initiate the embryonic coronary developmental program and epicardial progenitor cell activation in adult mice in vivo. J. Mol. Cell Cardiol. 2009; 46(5): 728-38.
  73. Sosne G., Qiu P., Christopherson P.L., Wheater M.K. Thymosin beta 4 suppression of corneal NFkB: A potential anti-inflammatory pathway. Exp. Eye. Res. 2007; 84(4): 663-9.
  74. Bollini S., Vieira J.M.N., Howard S. et al. Re-activated adult epicardial progenitor cells are a heterogeneous population molecularly distinct from their embryonic counterparts. Stem Cells Dev. 2014; 23(15): 1719-30.
  75. Sun-Wada G.H., Wada Y., Futai M. Vacuolar H+ pumping ATPases in luminal acidic organelles and extracellular compartments: common rotational mechanism and diverse physiological roles. J. Bioenerg. Biomembr. 2003; 35(4): 347-58.
  76. Widera C., Horn-Wichmann R., Kempf T. et al. Circulating concentrations of follistatin-like 1 in healthy individuals and patients with acutecoronary syndrome as assessed by an immunoluminometric sandwich assay. Clin. Chem. 2009; 55(10): 1794-800.
  77. El-Armouche A., Ouchi N., Tanaka K. et al. Follistatin-like 1 in chronic systolic heart failure: a marker of left ventricular remodeling. Circ. Heart Fail. 2011; 4(5): 621-7.
  78. Tanaka K., Valero-Munoz M., Wilson R.M. et al. Follistatin-Like 1 Regulates Hypertrophy in Heart Failure With Preserved Ejection Fraction. JACC Basic Transl. Sci. 2016; 1(4): 207-21.
  79. Oshima Y., Ouchi N., Sato K. et al. Follistatin-like 1 is an Akt-regulated cardioprotective factor that is secreted by the heart. Circ. 2008; 117(24): 3099-108.
  80. Ogura Y., Ouchi N., Ohashi K. et al. Therapeutic impact of follistatin-like 1 on myocardial ischemic injury in preclinical models. Circ. 2012; 126(14): 1728-38.
  81. Ouchi N., Asaumi Y., Ohashi K. et al. DIP2A functions as a FSTL1 receptor. J. Biol. Chem. 2010; 285(10): 7127-34.
  82. Corda S., Mebazaa A., Gandolfini M.P. et al. Trophic effect of human pericardial fluid on adult cardiac myocytes: differential role of fibroblast growth factor-2 and factors related to ventricular hypertrophy. Circ. Res. 1997; 81(5): 679-87.
  83. Iwakura A., Fujita M., Ikemoto M. et al. Myocardial ischemia enhances the expression of acidic fibroblast growth factor in human pericardial fluid. Heart Vessels 2000; 15(3): 112-6.
  84. Yoneda T., Fujita M., Kihara Y. et al. Pericardial fluid from patients with ischemic heart disease accelerates the growth of human vascular smooth muscle cells. Jpn. Circ. J. 2000; 64(7): 495-8.
  85. Sulaiman R.S., Merrigan S., Quigley J. et al. A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy. Sci. Rep. 2016; 6(1): 25509.
  86. Stankunas K., Ma G.K., Kuhnert F.J. et al. VEGF signaling has distinct spatiotemporal roles during heart valve development. Dev. Biol. 2010; 347(2): 325-36.
  87. Porrello E.R., Mahmoud A.I., Simpson E. et al. Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family. PNAS USA 2013; 110(1): 187-92.
  88. Дергилев К.В., Цоколаева З.И., Белоглазова И.Б. и др. Интрамио-кардиальное введение резидентных C-KIT+-прогениторных клеток сердца вызывает активацию прогениторных клеток эпикарда и стимулирует васкуляризацию миокарда после инфаркта. Гены и клетки 2018; 13(1): 75-81.
  89. Дергилев К.В., Цоколаева З.И., Белоглазова И.Б. и др. Сравнительная эффективность эпикардиальной трансплантации прогениторных клеток сердца в виде клеточных пластов и интрамиокардиальных инъекций при стимуляции регенеративных процессов в постинфарктном сердце. Кардиология 2019; 59(5): 53-60.
  90. Qin H., Zhao A., Zhang C., Fu X. Epigenetic Control of Reprogramming and Transdifferentiation by Histone Modifications. Stem Cell Rev. Rep. 2016; 12(6): 708-20.
  91. Bargehr J., Ong L.P., Colzani M. et al. Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration. Nat. Biotechnol. 2019; 37(8): 895-906.
  92. Menasché P. Cell therapy trials for heart regeneration - lessons learned and future directions. Nat. Rev. Cardiol. 2018; 15(11): 659-71.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2020 Eco-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: 

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies