HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/H474    most recent 00922.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shimojo, N. Articles by Miyauchi, T. Search for Related Content PubMed PubMed Citation Articles by Shimojo, N. Articles by Miyauchi, T.

Contributory role of VEGF overexpression in endothelin-1-induced cardiomyocyte hypertrophy

¹Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan; ²Center for Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, and ³Department of Pharmacology, School of Medicine, University of Toyama, Toyama, Japan

Submitted 25 August 2006 ; accepted in final form 16 March 2007

Although endothelin-1 (ET-1) stimulates vascular endothelial growth factor (VEGF) expression in a variety of cells, including endothelial cells and vascular smooth muscle cells, the effects of ET-1 on expression of VEGF and its receptors in cardiomyocytes are unknown. In the present study, we found that treatment of neonatal rat cardiomyocytes with ET-1 for 24 h resulted in upregulation of VEGF and its two principal receptors, fetal liver kinase 1 and fms-like tyrosine kinase 1, in a concentration-dependent manner (10^–12 to 10^–6 M). ET-1 treatment also caused significant cardiomyocyte hypertrophy, as indicated by increases in cell surface area and [¹⁴C]leucine uptake by cardiomyocytes. Treatment with TA-0201 (10^–6 M), an ET_A-selective blocker, eliminated ET-1-induced overexpression of VEGF and its receptors as well as cardiomyocyte hypertrophy. Treatment with VEGF neutralizing peptides (5–10 µg/ml) partially but significantly inhibited ET-1-induced cardiomyocyte hypertrophy. These results suggest that ET-1 treatment of cardiomyocytes promotes overexpression of VEGF and its receptors via activation of ET_A receptors, and consequently the upregulated VEGF signaling system appears to contribute, at least in part, to ET-1-induced cardiomyocyte hypertrophy.

ET_A receptor; hypoxia-inducible factor; VEGF neutralizing peptides

This article has been cited by other articles:

				S. B. Marko and D. H. Damon VEGF promotes vascular sympathetic innervation Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2646 - H2652. [Abstract] [Full Text] [PDF]