title: Clinical and experimental evidence of prostaglandin E1-induced angiogenesis in the myocardium of patients with ischemic heart disease.
abstract: OBJECTIVE
  Prostaglandin E1 (PGE-1) is a potent vasodilative agent which has been used to bridge patients with chronic heart failure listed for heart transplantation (HTX). In various experimental settings PGE-1 appears to stimulate angiogenesis by inducing vascular endothelial growth factor expression. This observational clinical study sought to investigate the angiogenic effects of PGE-1 in the failing human heart.
  
  
  METHODS
  Neovascularization was investigated in 14 explanted hearts from patients with ischemic cardiomyopathy (ICMP) who had been bridged to HTX with PGE-1 (8+/-1 mg/kg/min, 97+/-75.6 days) and compared with 14 hearts who did not receive PGE-1 prior to HTX. In three sectional areas obtained from the left ventricular wall CD34, von Willebrand factor (vWf), nuclear Ki67 (MIB-1), and VEGF were quantified by immunohistochemistry to estimate capillary density and endothelial cell proliferation. Additionally, to investigate a possible angiogenic effect of PGE-1 in vitro, cultured human coronary artery smooth muscle cells (HCASMCs) were treated with PGE-1.
  
  
  RESULTS
  PGE-1-treated patients had significantly more CD34- and vWf-positive cells in the subepicardium (both P<0.01), myocardium (both P<0.0001) and subendocardium (P<0.01 and P<0.001) as compared to the nonPGE-1 group. Proliferative endothelial activity expressed by the presence of MIB-1- and VEGF-positive cells (both P<0.0001 in all layers) was increased more than twofold. Addition of PGE-1 to HCASMCs in cell culture resulted in a significant increase in VEGF production (164.0+/-19.7 pg/10(5) cells/24 h, P<0.005) as compared to the control cell line (66.6+/-8.7 pg/10(5) cells/24 h, P<0.005).
  
  
  CONCLUSIONS
  Our data demonstrate that PGE-1 is a potent stimulator of angiogenesis via upregulation of VEGF expression. The induction of therapeutic angiogenesis in patients with severe ICMP might explain the favorable clinical outcome in PGE-1 treated patients until HTX.
authors.affiliation: Department of Cardiology, University of Vienna, Vienna, Austria. mohammad.mehrabi@univie.ac.at
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Mehrabi
authors.forename: Nermin
authors.initials: N
authors.lastname: Serbecic
authors.forename: Forouzan
authors.initials: F
authors.lastname: Tamaddon
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaun
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.forename: Richard
authors.initials: R
authors.lastname: Pacher
authors.forename: Thomas
authors.initials: T
authors.lastname: Wild
authors.forename: Gerhard
authors.initials: G
authors.lastname: Mall
authors.forename: Johann
authors.initials: J
authors.lastname: Wojta
authors.forename: Helmut-D
authors.initials: HD
authors.lastname: Glogar
mesh_terms: D000328:Adult; D000368:Aged; D000527:Alprostadil / Q000494:pharmacology*; D018952:Antigens, CD34 / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D003331:Coronary Vessels / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000378:metabolism; D005260:Female; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D009687:Nuclear Proteins / Q000378:metabolism; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D008222:Lymphokines; D009687:Nuclear Proteins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor; D000527:Alprostadil