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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:624.)
© 2000 American Heart Association, Inc.

Vascular Biology

Enhanced Expression of Osteopontin in Human Diabetic Artery and Analysis of Its Functional Role in Accelerated Atherogenesis

Minoru Takemoto; Koutaro Yokote; Motonobu Nishimura; Takashi Shigematsu; Toshio Hasegawa; Shigeyuki Kon; Toshimitsu Uede; Taro Matsumoto; Yasushi Saito; Seijiro Mori

From the Second Department of Internal Medicine (M.T., K.Y., T.M., Y.S., S.M.), School of Medicine, Chiba University, and the Department of Internal Medicine (M.N., T.S., T.H.), Sakura National Hospital, Chiba, Japan; and the Section of Immunopathogenesis (S.K., T.U.), Institute of Immunological Science, Hokkaido University, Hokkaido, Japan.

Correspondence to Minoru Takemoto, Second Department of Internal Medicine, School of Medicine, Chiba University, 1-8-1 Inohana, Chiba 260-0856, Japan. E-mail mtakemo{at}intmed02.m.chiba-u.ac.jp

Abstract—We have previously reported that high glucose stimulates osteopontin (OPN) expression through protein kinase C–dependent pathways as well as hexosamine pathways in cultured rat aortic smooth muscle cells. The finding prompted us to study in vivo expression of OPN in diabetes mellitus. In the present study, we found by immunohistochemistry that medial layers of the carotid arteries of streptozotocin-induced diabetic rats and the forearm arteries of diabetic patients stained positively for OPN antibodies, whereas the staining from arteries of control rats and nondiabetic patients was negative. We also found that OPN stimulated the migration and enhanced platelet-derived growth factor (PDGF)-mediated DNA synthesis of cultured rat aortic smooth muscle cells. OPN and PDGF synergistically activated focal adhesion kinase as well as extracellular signal–regulated kinase; this finding seems to explain the OPN-induced enhancement of PDGF-mediated DNA synthesis. Taken together, our present results raise a possibility that OPN plays a role in the development of diabetic vascular complications.

Key Words: diabetic macroangiopathy • osteopontin • platelet-derived growth factor • vascular smooth muscle cells

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