Anti-heat shock protein 70 autoantibody epitope changes and BD091 promotes atherosclerosis in rats.
It has been previously reported that the plasma levels of autoantibodies against heat shock protein 70 (HSP70) are elevated in atherosclerosis. The aim of the present study was to elucidate whether anti-HSP70 antibodies are involved in the pathogenesis of atherosclerosis. To determine this, we chose rats as an atherosclerosis model. Titers of plasma anti-HSP70 autoantibody were determined by ELISA. After the intravenous administration of antibody into the tail, the damaged areas of aorta were stained with Evans Blue, atheromatous plaque were stained by Oil Red O, and then they were measured and quantified with AxioVision computer software. The number of macrophages ([Formula: see text]), smooth muscle cells (SMCs), and T cells were determined by immunocytochemistry. The level of anti-HSP70 IgG1 antibody was apparently increased in the AS group at the tenth week, and one hybridoma of HSP70 antibody (BD091, IgG1, recognizing C-terminal) had the same binding epitope as plasma anti-HSP70 autoantibodies. After intravenous administration, the lesion area of aorta with BD091 was significantly larger than those of IgG(mouse) and SPA-810. Moreover, injection of BD091 resulted in significant endothelium damage, followed by a greater accumulation of [Formula: see text], T cells, and SMCs in lesions than in the control. In conclusion, BD091 reaction with HSP70 expressed on arterial endothelial cells inducing endothelium damage triggers the inflammatory response in the vessel wall that accelerates atherosclerosis in rats. BD091 shares the same binding epitope with HSP70 autoantibodies. These data indicated that a specific epitope of anti-HSP70 autoantibody participated in the pathogenesis of atherosclerosis.
Leng
Xue
X
Department of Stress Medicine, Institute of Health and Environmental Medicine, 1 Da Li Road, Tianjin, 300050, China.
Zhan
Rui
R
Wang
Yang
Y
Liu
Xiaohua
X
Gong
Jingbo
J
Gao
Xiujie
X
Wu
Lei
L
Wang
Liqun
L
Zhao
Yun
Y
Wang
Xinxing
X
Zhang
Zhiqing
Z
Pang
Wei
W
Qian
Lingjia
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000633:toxicity*; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology / Q000633:toxicity*; D004730:Endothelium, Vascular / Q000473:pathology; D000939:Epitopes / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000939:Epitopes; D018840:HSP70 Heat-Shock Proteins