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This Article Full Text Full Text (PDF) All Versions of this Article: 289/5/H2066    most recent 00147.2005v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Haider, D. G. Articles by Baghestanian, M. Search for Related Content PubMed PubMed Citation Articles by Haider, D. G. Articles by Baghestanian, M.

PGE₁ analog alprostadil induces VEGF and eNOS expression in endothelial cells

¹Department of Angiology, ²Department of Cardiology, ³Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria

Submitted 14 February 2005 ; accepted in final form 31 May 2005

Endothelial nitric oxide synthase (eNOS), VEGF, and hypoxia-inducible factor 1- (HIF-1) are important regulators of endothelial function, which plays a role in the pathophysiology of heart failure (HF). PGE₁ analog treatment in patients with HF elicits beneficial hemodynamic effects, but the precise mechanisms have not been investigated. We have investigated the effects of the PGE₁ analog alprostadil on eNOS, VEGF, and HIF-1 expression in human umbilical vein endothelial cells (HUVEC) using RT-PCR and immunoblotting under normoxic and hypoxic conditions. In addition, we studied protein expression by immunohistochemical staining in explanted hearts from patients with end-stage HF, treated or untreated with systemic alprostadil. Alprostadil causes an upregulation of eNOS and VEGF protein and mRNA expression in HUVEC and decreases HIF-1. Hypoxia potently increased eNOS, VEGF, and HIF-1 synthesis. The alprostadil-induced upregulation of eNOS and VEGF was prevented by inhibition of MAPKs with PD-98056 or U-0126. Consistently, the expression of eNOS and VEGF was increased, and HIF-1 was reduced in failing hearts treated with alprostadil. The potent effects of alprostadil on endothelial VEGF and eNOS synthesis may be useful for patients with HF where endothelial dysfunction is involved in the disease process.

endothelial nitric oxide synthase; prostaglandin E mitogen-activated protein kinases; vascular endothelial growth factor