Revascularization of myocardial scar tissue following prostaglandin E1-therapy in patients with ischemic heart disease.
Prostaglandin E1 (PGE-1) treatment has proved to stimulate angiogenesis in vital non-infarcted myocardium of patients with ischemic cardiomyopathy (ICMP). We investigated infarcted myocardial tissue for a possible angiogenic response to PGE-1. Neovascularization was investigated in infarcted areas of 12 hearts explanted from patients with ICMP who had been treated with PGE-1 before heart transplantation (HTX). In transmural sections containing myocardial scar tissue, CD34 and VEGF were immunohistochemically quantified to estimate capillary density and the extent of angiogenesis. To investigate a possible effect of PGE-1 on collagen turnover, the collagen content was determined in myocardial scar tissue by assessing the intensity of the area positively stained with sirius red. PGE-1-treated patients had significantly more CD34- and VEGF-positive cells in infarcted areas, and showed a significant reduction in collagen content as compared with the non-PGE-1 group (CD34: 120.3 +/- 6.1 vs. 47.7 +/- 6.1 capillary profiles/mm2; VEGF: 52.8 +/- 5.6 vs. 24.0 +/- 4.8 capillary profiles/mm2, and collagen content: 2.18 +/- 0.4 eU vs. 3.59 +/- 0.38 eU). Our data demonstrate that PGE-1 stimulates angiogenesis by upregulating VEGF expression, and reduces fibrosis in cardiac scar tissue of ischemic origin. The induction of therapeutic angiogenesis in vital and at sites of putative dead myocardial scar tissue, along with the hemodynamic improvement in patients with severe ICMP, might explain the favorable clinical outcome in PGE-1-treated patients before HTX.
Mehrabi
Mohammad Reza
MR
Department of Cardiology, University of Vienna, Austria. mohammad.mehrabi@univie.ac.at
Serbecic
Nermin
N
Tamaddon
Forouzan
F
Huber
Kurt
K
Pacher
Richard
R
Grimm
Michael
M
Glogar
Helmut-D
HD
D000527:Alprostadil / Q000627:therapeutic use*; D018952:Antigens, CD34 / Q000378:metabolism; D002921:Cicatrix; D003094:Collagen / Q000032:analysis; D005260:Female; D005355:Fibrosis / Q000473:pathology; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy*; D009204:Myocardial Revascularization; D009206:Myocardium / Q000737:chemistry / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D018952:Antigens, CD34; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; D000527:Alprostadil