Angiogenesis stimulation in explanted hearts from patients pre-treated with intravenous prostaglandin E-1

Background: Prostaglandin E, (PGE,) is a potent vasodilator and induces ang iogenesis in animal tissues. Previous clinical studies demonstrated that PG E, improves hemodynamic parameters in patients with heart failure listed fo r heart transplantation (HTX). Therefore, we designed a retrospective immun ohistochemistry study to investigate various markers of angiogenesis using hearts explanted from PGE(1)-treated patients with idiopathic dilated cardi omyopathy (IDCM). Methods and Results: We investigated neovascularization in 18 hearts explan ted from patients with IDCM: 9 patients received treatment with chronic inf usions of PGE, for end-stage heart failure before HTX, whereas the remainin g patients with IDCM did not receive PGE, and served as controls. We used i mmunoreactivity against CD34, von Willebrand factor (vWf), vascular endothe lial growth factor (VEGF), and MIB-1 (Ki-67) to quantify angiogenesis, and used sirius red staining to determine the degree of fibrosis. Compared with the control group, PGE(1)-treated patients had significantly more CD34-, v Wf- and MIB-1-positive cells in the sub-endocardium, myocardium and subepic ardium (p < 0.01). The degree of fibrosis in the hearts of PGE(1)-treated p atients was significantly lower than in control patients (p < 0.05), but we did not see any difference in the percentage of muscle mass. Finally, thro ughout the ventricles, we found significantly more VEGF-positive capillarie s in the PGE, group (p < 0.0001). Conclusions: The data suggest that PGE, could be a potent inducer of angiog enesis and the angiogenic factor VEGF, and could cause reduced fibrosis in the failing human heart.