[王晓亮; 彭国文] School of Chemistry and Chemical Engineering, University of South China, Hengyang, China;[杨锦然; 黄红; 周归] Wang Chuanshan College, University of South China, Hengyang, China;[彭国文] School of Resources and Safety Engineering, Central South University, Changsha, China;[胡南; 肖方竹; 彭国文; 丁德馨; 张志军] Key Discipline Laboratory for National Defence for Biotechnology in Uranium Mining and Hydrometallurgy, University of South China, Hengyang, China
School of Chemistry and Chemical Engineering, University of South China, Hengyang, China
Progress in Biochemistry and Biophysics,2013年40(9):834-844 ISSN：1000-3282
[Gu Hong-Feng] Univ South China, Dept Physiol, Hengyang 421001, Peoples R China.;[Gu Hong-Feng; Yang Yong-Zong] Key Lab Arteriosclerol Hunan Prov, Hengyang 421001, Peoples R China.;[Jiang Jian-Hong] Nanhua Univ, Chuanshan Coll, Hengyang 421001, Peoples R China.;[Tong Qiao-Zhen; Liao Duan-Fang] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha 410208, Hunan, Peoples R China.
[Gu Hong-Feng] Univ South China, Dept Physiol, Hengyang 421001, Peoples R China.
The effects of glycoprotein (GP) Ⅱb/Ⅲa inhibitors on the development of the atherosclerotic process has received scant attention. To investigate whether GP Ⅱb/Ⅲa blockade influences atherosclerosis lesion and HMGB-1/TLR4 signaling, we compared plaque formation in ApoE~(-/-) mice: control group (n=10); IgG group (n=10, 50 μg) and GP Ⅱb/Ⅲa mAb group (n=10, 50 μg). All mice were fed on a Western diet (10% fat and 1.25% cholesterol) for 10 weeks. GP Ⅱb/Ⅲa blockade significantly decreased the atherosclerotic lesion and platelet adhesion to the vessel wall. Immunohistochemistry analysis showed that blocking GP Ⅱb/Ⅲa diminished MOMA-2 and VCAM-1 expression in aortic plaque in ApoE~(-/-) mice. Western blot results indicated that HMGB-1, TLR4, and NF-κB levels were markedly reduced in arteries of ApoE-/- mice treated with GP Ⅱb/Ⅲa mAb (P < 0.05). Moreover, GP Ⅱb/Ⅲa mAb decreased plasma HMGB-1, IL-1β, TNF-α and MCP-1 concentrations. Our findings demonstrated that GP Ⅱb/Ⅲa mAb significantly decreased atherosclerotic lesions and HMGB-1, TLR4 and NF-κB expression in ApoE~(-/-) mice (P < 0.05). The present study has suggested a possibility that GP Ⅱb/Ⅲa blockade attenuates atherosclerosis by inhibiting the HMGB-1/TLR4 pathway..