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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:2041-2048.)
© 1999 American Heart Association, Inc.

Vascular Biology

Angiostatin Binds to Smooth Muscle Cells in the Coronary Artery and Inhibits Smooth Muscle Cell Proliferation and Migration In Vitro

Jennifer J. Walter; David C. Sane

From the Section of Cardiology, Wake Forest University School of Medicine, Winston-Salem, NC.

Correspondence to David C. Sane, MD, Section of Cardiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1045. E-mail dsane{at}wfubmc.edu

Abstract—Angiostatin is an inhibitor of angiogenesis that is known to reduce endothelial cell proliferation and consequently prevent the progression of tumor metastases. However, the modest effect of angiostatin on endothelial cell proliferation raises the possibility that angiostatin might exert its effects on other cells. To determine the cellular distribution of angiostatin binding in tissues with neovasculature (atherosclerotic coronary arteries), we developed a fusion protein consisting of placental alkaline phosphatase and the first 3 kringles of plasminogen. Angiostatin binding colocalized with smooth muscle cells and could be inhibited by a 50-fold molar excess of plasminogen and 10 mmol/L -amino-n-caproic acid. The fusion protein also bound to smooth muscle cells in culture. Angiostatin inhibited hepatocyte growth factor–induced proliferation and migration of smooth muscle cells, suggesting that they are a target for the antiangiogenic effect of angiostatin.

Key Words: angiostatin • angiogenesis • plasminogen • hepatocyte growth factor • smooth muscle cells

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