Cytoplasmic Expression and Extracellular Deposition of an Antiangiogenic Factor, Pigment Epithelium-Derived Factor, in Human Atherosclerotic Plaques

Abstract

Objective-To assess the expression and distribution of a neurotrophic/antiangiogenic factor, pigment epithelium-derived factor (PEDF), related to angiogenesis that is a possibly key event during atherogenesis in human atherosclerotic plaques. Methods and Results-Twenty fresh aortic samples were used for reverse-transcription polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry (IHC). In addition, 80 stocked paraffin blocks of coronary arteries from 40 autopsy cases were also used. IHC revealed divergent staining patterns for PEDF in both the aortas and the coronary arteries tested, ie, "cytoplasmic staining" or "extracellular deposition," were observed, respectively. In the areas showing cytoplasmic staining, double PEDF was expressed in a majority of the foamy macrophages and in some smooth muscle cells, and the PEDF-positive cell frequency was positively correlated with that of microvessels in a cell-rich area in the coronary arteries (PϽ0.0001). Inversely, extracellular deposition of PEDF was seen in acellular areas and was negatively correlated with the number of microvessels (Pϭ0.0003). Conclusions-These

Proteomics Analysis of Human Coronary Atherosclerotic Plaque

“…While this manuscript was in preparation PEDF expression was reported in the atherosclerotic plaque in the aorta and coronary arteries (30). Mass spectrometry detection and IHC staining observed in our study further confirmed the presence of PEDF in the human plaque, suggesting that the factor might play a role in the evolution of the disease.…”

Late Outgrowth Endothelial Cells Derived From Wharton Jelly in Human Umbilical Cord Reduce Neointimal Formation After Vascular Injury

“…25 PEDF exerts its antiangiogenic activity in human atherosclerotic plaques. 26 Moreover, PEDF plays a protective role against atherosclerosis through its antioxidative properties because it prevents the advanced glycation end product-elicited endothelial nitric oxide synthase reduction 27 and can inhibit occlusive thrombus formation by blocking platelet activation and aggregation. 28 Recently, it has also been shown to strongly inhibit PDEF-induced SMC proliferation and migration by blocking the generation of reactive oxygen species and to block neointimal hyperplasia in balloon-injured rat carotid arteries.…”

From Lipid Retention to Immune-Mediate Inflammation and Associated Angiogenesis in the Pathogenesis of Atherosclerosis

“…On the other hand, atherosclerotic lesions responsible for vascular occlusion are themselves associated with angiogenesis within the vessel wall. An imbalance between the inducers and inhibitors, with a predominance of the former, is essential for the induction of neovascularization in the atherosclerotic arterial wall, and the angiogenic switch may be the consequence of a down-regulation in the expression of two or even more angiogenesis inhibitors 63) . Several angiogenic and antiangiogenic factors events such as myocardial infarction and stroke.…”