title: Clinical benefit of prostaglandin E1-treatment of patients with ischemic heart disease: stimulation of therapeutic angiogenesis in vital and infarcted myocardium.
abstract: New evidence suggests that Prostaglandin E1 (PGE-1) stimulates myocardial angiogenesis in human chronic ischemic myocardium. We sought to investigate whether PGE-1 may participate in the process of neoangiogenesis within the myocardial infarct scar. Neovascularization was investigated in 14 explanted hearts from patients with ischemic cardiomyopathy, who had been bridged to heart transplantation (HTX) with PGE-1 and compared with 14 hearts from patients who did not receive PGE-1 prior to HTX. In transmural sections obtained from the left ventricular wall and containing myocardial scar tissue, CD34 and vascular endothelial growth factor (VEGF) were quantified immunohistochemically to estimate capillary density and amount of angiogenesis. Additionally, to assess the hypoxic state of myocardium of the infarct border zone, hypoxia inducible factor 1-alpha (HIF-1alpha) was determined by immunohistochemistry and quantified by means of planimetric analysis. PGE-1-treated patients had significantly more CD34-and VEGF-positive cells in infarct areas as compared to nonPGE-1 group, respectively (CD34: 116.7 +/- 5.9 vs. 45.1 +/- 5.2 capillary profiles/mm(2), P < 0.001, and VEGF: 48.3 +/- 4.9 vs. 22.9 +/- 4.7 capillary profiles/mm(2)). HIF-1alpha enrichment (in %) as well as staining intensity (in estimated units (eU)) was significantly decreased in PGE-1-treated as compared to non-treated controls (enrichment: 11.3 +/- 2.5% vs. 19.4 +/- 4.36%; staining intensity: 0.95 +/- 0.3 vs. 1.97 +/- 0.44 eU). Our data demonstrate that PGE-1 stimulates neoangiogenesis in infarct areas adjacent to viable myocardium, via upregulation of VEGF expression. The induction of therapeutic angiogenesis along with the improved hypoxic state of chronic ischemic myocardial tissue might explain the favorable clinical outcome in PGE-1 treated patients.
authors.affiliation: Department of Cardiology, General Hospital (AKH), University of Vienna, Postfach 120, Währinger Gürtel 18-20, 1090, Vienna, Austria. mohamad.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: Richard
authors.initials: R
authors.lastname: Pacher
authors.forename: Reinhard
authors.initials: R
authors.lastname: Horvath
authors.forename: Gerhard
authors.initials: G
authors.lastname: Mall
authors.forename: Helmut D
authors.initials: HD
authors.lastname: Glogar
mesh_terms: D000527:Alprostadil / Q000627:therapeutic use*; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers; D001794:Blood Pressure / Q000502:physiology; D002196:Capillaries / Q000473:pathology; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011651:Pulmonary Artery / Q000502:physiology; D011669:Pulmonary Wedge Pressure / Q000502:physiology; D013268:Stimulation, Chemical; D014157:Transcription Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D014665:Vasodilator Agents; D000527:Alprostadil