Prostaglandin E1 induces vascular endothelial growth factor-1 in human adult cardiac myocytes but not in human adult cardiac fibroblasts via a cAMP-dependent mechanism

Prostaglandin E1 (PGE1) 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 PGE1 was shown to stimulate angiogenesis in animal models. Recently we showed that PGE1-induced angiogenesis in hearts of patients with ischemic heart disease. We proposed that the angiogenic action of PGE1 is mediated by vascular endothelial growth factor (VEGF). In the present paper we studied a possible effect of PGE1 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 PGE1. We also aimed to delineate mechanisms involved in a possible regulation of VEGF-1 by PGE1 in these cells. When HACM, isolated from human myocardial tissue, were treated with PGE1, 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 PGE1 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 PGE1 on VEGF-1 production was seen. If this effect of PGE1 is also operative in the in vivo situation, one could speculate that cardiac myocytes could be a cellular source of PGE1-induced VEGF-1 expression in patients treated with this drug.