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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1938.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

Hiromitsu Baba; Yoshikazu Yonemitsu; Toshiaki Nakano; Mitsuho Onimaru; Masanori Miyazaki; Yasuhiro Ikeda; Shinji Sumiyoshi; Yasuji Ueda; Mamoru Hasegawa; Ichiro Yoshino; Yoshihiko Maehara; Katsuo Sueishi

From the Division of Pathophysiological and Experimental Pathology (H.B., Y.Y., T.N., M.O., M.M., Y.I., S.S., K.S.), the Department of Pathology and Department of Surgery and Science (H.B., I.Y., Y.M.), Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and DNAVEC Corporation (Y.Y., Y.U., M.H.), Tsukuba, Ibaraki, Japan.

Correspondence to Dr Yoshikazu Yonemitsu, Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail yonemitu{at}pathol1.med.kyushu-u.ac.jp

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 (P<0.0001). Inversely, extracellular deposition of PEDF was seen in acellular areas and was negatively correlated with the number of microvessels (P=0.0003).

Conclusions— These results suggest that PEDF may function as an antiangiogenic factor when it is deposited onto the extracellular matrix. Thus, PEDF may play a significant role in determining the balance of angiogenesis/ antiangiogenesis during atherogenesis.

To obtain the evidence of antiangiogenic factor in atherosclerotic plaque, we investigated the localization of pigment epithelium-derived factor (PEDF). Extracellular deposition of PEDF was negatively correlated with the number of microvessels, suggesting that PEDF functions as an antiangiogenic factor when it is deposited onto the extracellular matrix in human subjects.

Key Words: angiogenesis • aorta • atherosclerosis • coronary artery • immunohistochemistry • pigment epithelium-derived factor

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