title: Cardiac endothelial cells express Wilms' tumor-1: Wt1 expression in the developing, adult and infarcted heart.
abstract: Myocardial infarction is the leading cause of death worldwide. Due to their limited regenerative capacity lost cardiomyocytes are replaced by a non-contractile fibrotic scar tissue. The epicardial layer of the heart provides cardiac progenitor cells during development. Because this layer regains embryonic characteristics in the adult heart after cardiac injury, it could serve as a promising source for resident cardiac progenitor cells. Wilms' tumor-1 (Wt1) is associated with the activation and reactivation of the epicardium and therefore potentially important for the differentiation and regenerative capacity of the epicardium. To gain more insight into the regulation of Wt1 we examined the spatiotemporal expression pattern of Wt1 during murine development and after cardiac injury. Interestingly, we found that Wt1 is expressed in the majority of the cardiac endothelial cells within the myocardial ventricular layer of the developing heart from E12.5 onwards. In the adult heart only a subset of coronary endothelial cells remains positive for Wt1. After myocardial infarction Wt1 is temporally upregulated in the endothelial cells of the infarcted area and the border zone of the heart. In vitro experiments show that endothelial Wt1 expression can be induced by hypoxia. We show that Wt1 is associated with endothelial cell proliferation: Wt1 expression is higher in proliferating endothelial cells, Wt1 knockdown inhibits the proliferation of endothelial cells, and Wt1 regulates CyclinD1 expression. Finally, endothelial cells lacking Wt1 are not capable to establish a proper vascular network in vitro. Together, these results suggest a possible role for Wt1 in cardiac vessel formation in development and disease.
authors: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Sjoerd N
authors: SN
authors: Duim
authors: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Kondababu
authors: K
authors: Kurakula
authors: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: M.J.T.H.Goumans@lumc.nl.
authors: Marie-José
authors: MJ
authors: Goumans
authors: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: B.P.T.Kruithof@lumc.nl.
authors: Boudewijn P T
authors: BP
authors: Kruithof
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D002465:Cell Movement; D049109:Cell Proliferation; D003094:Collagen / Q000737:chemistry; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004338:Drug Combinations; D004622:Embryo, Mammalian; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007797:Laminin / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D010496:Pericardium / Q000378:metabolism* / Q000473:pathology; D011509:Proteoglycans / Q000737:chemistry; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D025721:WT1 Proteins
chemical_list: C530105:Ccnd1 protein, mouse; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D012097:Repressor Proteins; D025721:WT1 Proteins; C000602896:WT1 protein, mouse; C059485:matrigel; D019938:Cyclin D1; D003094:Collagen
keywords: Cardiac development; Cardiac regeneration; Endothelial cells; Epicardium; Myocardial infarction; Wilm's tumor-1