부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.atherosclerosis.2005.02.032 Byline: Yu-ichiro Sakamoto (a), Akira Miyazaki (b), Harumi Tamagawa (a), Guo-Ping Wang (a), Seikoh Horiuchi (a) Abstract: Oxidized LDL (Ox-LDL) plays atherogenic roles, whereas thrombospondin-1 (TSP-1) is thought to be anti-atherogenic through activation of TGF-[beta] that contributes to plaque stabilization. Ox-LDL was prepared by incubating of human LDL with CuSO.sub.4. Effect of Ox-LDL on TSP-1-induced TGF-[beta] activation was examined in the present study. Incubation of Ox-LDL with mouse peritoneal macrophages for 3 days resulted in reduction in amounts of active TGF-[beta] in the culture medium by 70-78% when compared with that of parallel incubation without Ox-LDL. TSP-1 could enhance conversion of latent TGF-[beta]1 into active TGF-[beta]1 in a cell-free system. This TSP-1-mediated latent TGF-[beta]1 activation was inhibited by 30% by Ox-LDL, suggesting the possible interaction of Ox-LDL with TSP-1. Incubation of TSP-1 with [.sup.125I]Ox-LDL or [.sup.125I]LDL, followed by immunoprecipitation with an anti-TSP-1 antibody demonstrated that a significant amount of [.sup.125I]Ox-LDL was co-precipitated with TSP-1 while precipitation of [.sup.125I]LDL was negligible. Furthermore, upon TSP-1-conjugated Sepharose 4B affinity chromatography, both [.sup.125I]Ox-LDL and [.sup.125I]latent TGF-[beta]1 bound to the affinity gel were eluted by unlabeled Ox-LDL. These findings indicate that Ox-LDL interacts with TSP-1 and suppresses subsequent TSP-1-dependent TGF-[beta] activation, revealing a novel atherogenic function of Ox-LDL. Author Affiliation: (a) Department of Medical Biochemistry, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan (b) Department of Biochemistry, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan