Vascular endothelial growth factor promotes cardiomyocyte differentiation of embryonic stem cells Journal Article
| Authors: | Chen, Y.; Amende, I.; Hampton, T. G.; Yang, Y.; Ke, Q.; Min, J. Y.; Xiao, Y. F.; Morgan, J. P. |
| Article Title: | Vascular endothelial growth factor promotes cardiomyocyte differentiation of embryonic stem cells |
| Abstract: | Embryonic stem cells (ESCs) overexpressing the vascular endothelial growth factor (VEGF) improve cardiac function in mouse models of myocardial ischemia and infarction by mechanisms that are poorly understood. Here we studied the effects of VEGF on cardiomyocyte differentiation of mouse ESCs in vitro. We used flow cytometry to determine the expression of α-myosin heavy chain (α-MHC), cardiac troponin I (cTn-I), and Nkx2.5 in differentiated ESCs. VEGF (20 ng/ml) significantly enhanced α-MHC, cTn-I, and Nkx2.5 expression in differentiated ESCs. Western blot analysis confirmed these findings. We found that VEGF receptor FMS-like tyrosine kinase-1 (Flt-1) and fetal liver kinase-1 (Flk-1) expression increased during ESC differentiation. Antibodies against Flk-1 totally blocked and against Flt-1 partially blocked VEGF-induced NKx2.5-positive-stained cells. The ERK inhibitor PD-098059 abolished VEGF-induced cardiomyocyte differentiation of ESCs. Our results suggest that VEGF promotes cardiomyocyte differentiation predominantly by ERK-mediated Flk-1 activation and, to a lesser extent, by Flt-1 activation. These findings may be of significance for stem cell and growth factor therapies to regenerate failing cardiomyocytes. Copyright © 2006 the American Physiological Society. |
| Keywords: | mitogen activated protein kinase; vasculotropin; controlled study; protein expression; vascular endothelial growth factor a; unclassified drug; nonhuman; flow cytometry; animal cell; mouse; animals; mice; vasculotropin receptor; stress activated protein kinase; embryonic stem cell; cell line; stem cell transplantation; cell differentiation; homeodomain proteins; enzyme activation; in vitro study; vasculotropin receptor 2; vascular endothelial growth factor receptor-2; transcription factors; gene expression regulation; western blotting; extracellular signal-regulated map kinases; flavonoids; homeodomain protein; vascular endothelial growth factor receptor-1; heart muscle cell; troponin i; vasculotropin receptor 1; protein antibody; receptor upregulation; map kinase kinase 4; myocytes, cardiac; 2 (2 amino 3 methoxyphenyl)chromone; myosin heavy chain alpha; cardiac-specific proteins; extracellular signal-regulated kinase; flt-1 and flk-1; homeobox protein nkx2; vasculotropin receptor 1 antibody; ventricular myosins |
| Journal Title: | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume: | 291 |
| Issue: | 4 |
| ISSN: | 0363-6135 |
| Publisher: | American Physiological Society |
| Date Published: | 2006-10-01 |
| Start Page: | H1653 |
| End Page: | H1658 |
| Language: | English |
| DOI: | 10.1152/ajpheart.00363.2005 |
| PUBMED: | 16699073 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 27" - "Export Date: 4 June 2012" - "CODEN: AJPPD" - "Source: Scopus" |
