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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:955.)
© 2001 American Heart Association, Inc.

Vascular Biology

Oxidized LDL Modulates Bax/Bcl-2 Through the Lectinlike Ox-LDL Receptor-1 in Vascular Smooth Muscle Cells

Hiroharu Kataoka; Noriaki Kume; Susumu Miyamoto; Manabu Minami; Masafumi Morimoto; Kazutaka Hayashida; Nobuo Hashimoto; Toru Kita

From the Departments of Geriatric Medicine (N.K., M. Minami, K.H., T.K.) and Neurosurgery (H.K., S.M., M. Morimoto, N.H.), Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Correspondence to Noriaki Kume, MD, PhD, Department of Geriatric Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. E-mail nkume{at}5fkuhp.kyoto-u.ac.jp

Abstract—Oxidized low density lipoprotein (Ox-LDL) induces apoptosis in vascular smooth muscle cells (VSMCs), which may increase atherosclerotic plaque instability. In this study, we examined the molecular mechanisms causing the Ox-LDL–induced apoptosis in VSMCs, especially focusing on the involvement of Bax/Bcl-2 and the lectinlike Ox-LDL receptor-1 (LOX-1). In cultured bovine aortic smooth muscle cells (BASMCs), Ox-LDL at high concentrations (>60 µg/mL) induced cell death as demonstrated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. DNA fragmentation was increased in BASMCs treated with high concentrations of Ox-LDL, indicating that the Ox-LDL–induced cell death in VSMCs was apoptosis. Ox-LDL upregulated LOX-1 expression through phosphorylation of extracellular signal–regulated kinase in BASMCs, and a neutralizing anti–LOX-1 monoclonal antibody, which can block LOX-1–mediated cellular uptake of Ox-LDL, prevented the Ox-LDL–induced apoptosis in BASMCs. This antibody also suppressed the increase in the Bax to Bcl-2 ratio induced by Ox-LDL in BASMCs. Furthermore, LOX-1 expression was well colocalized with Bax expression in the rupture-prone shoulder areas of human atherosclerotic plaques in vivo. LOX-1 may play an important role in Ox-LDL–induced apoptosis in VSMCs by modulating the Bax to Bcl-2 ratio. These molecular mechanisms may be involved in destabilization and rupture of atherosclerotic plaques.

Key Words: atherosclerosis • lipoproteins • receptors • apoptosis

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