title: 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.
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.
authors.affiliation: Department of Internal Medicine II, Medical University Vienna, and the Ludwig Boltzmann Foundation for Cardiovascular Research, Waehringer Guertel 18-20, Vienna A-1090, Austria.
authors.forename: Thomas Werner
authors.initials: TW
authors.lastname: Weiss
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Mehrabi
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaun
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Zorn
authors.forename: Stefan Peter
authors.initials: SP
authors.lastname: Kastl
authors.forename: Walter Stefan
authors.initials: WS
authors.lastname: Speidl
authors.forename: Stefan
authors.initials: S
authors.lastname: Pfaffenberger
authors.forename: Gersina
authors.initials: G
authors.lastname: Rega
authors.forename: Helmut Dietmar
authors.initials: HD
authors.lastname: Glogar
authors.forename: Gerald
authors.initials: G
authors.lastname: Maurer
authors.forename: Richard
authors.initials: R
authors.lastname: Pacher
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.forename: Johann
authors.initials: J
authors.lastname: Wojta
mesh_terms: D000527:Alprostadil / Q000378:metabolism / Q000502:physiology*; D001011:Aorta / Q000166:cytology; D002455:Cell Division; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D017931:DNA Primers; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D012333:RNA, Messenger; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000527:Alprostadil; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide