Prostaglandin E 1 induces vascular endothelial growth factor-1 in human adult cardiac myocytes but not in human adult cardiac fibroblasts via a cAMP-dependent mechanism

Abstract

Prostaglandin E 1 (PGE 1) has been used to treat pulmonary hypertension and peripheral artery occlusive disease and has been successfully employed for pharmacological bridging to transplantation in patients with chronic end-stage heart failure. In addition to its vasoactive effects PGE 1 was shown to stimulate angiogenesis in animal models. Recently we showed that PGE 1-induced angiogenesis in hearts of patients with ischemic heart disease. We proposed that the angiogenic action of PGE 1 is mediated by vascular endothelial growth factor (VEGF). In the present paper we studied a possible effect of PGE 1 on the expression of VEGF-1 in cultured human adult cardiac myocytes (HACM) and cultured human adult cardiac fibroblasts (HACFB), respectively, to identify a cellular source of VEGF-1 in patients treated with PGE 1. We also aimed to delineate mechanisms involved in a possible regulation of VEGF-1 by PGE 1 in these cells. When HACM, isolated from human myocardial tissue, were treated with PGE 1, a significant up to 3-fold increase in VEGF-1 production could be observed. These results could be confirmed on the level of specific mRNA expression as determined by real-time polymerase chain reaction. The effect of PGE 1 on VEGF-1 expression could be blocked by H089, an inhibitor of cAMP-dependent protein kinase A. In HACFB, also isolated from human myocardial tissue, no effect of PGE 1 on VEGF-1 production was seen. If this effect of PGE 1 is also operative in the in vivo situation, one could speculate that cardiac myocytes could be a cellular source of PGE 1-induced VEGF-1 expression in patients treated with this drug.