© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Clinical and experimental evidence of prostaglandin E1-induced angiogenesis in the myocardium of patients with ischemic heart disease
aDepartment of Cardiology, University of Vienna, Vienna, Austria
bDepartment of Surgery, University of Vienna, Vienna, Austria
cDepartment of Pathology, Darmstadt, Germany
mohammad.mehrabi{at}univie.ac.at
* Corresponding author. Department of Cardiology, University of Vienna, Postfach 120, Waehringer Gürtel 18–20, A-1090 Vienna, Austria. Tel.: +43-1-40400-4614; fax: +43-1-408-1148.
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/105 cells/24 h, P<0.005) as compared to the control cell line (66.6±8.7 pg/105 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.
KEYWORDS Angiogenesis; Cardiomyopathy; Prostaglandins; Growth factors; Ischemia
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