title: Diet-induced elevation of circulating HSP70 may trigger cell adhesion and promote the development of atherosclerosis in rats.
abstract: Although accumulating evidence indicates that heat shock protein 70 (HSP70) could be secreted into plasma and its levels have been found to have an ambiguous association with atherosclerosis, our knowledge for the exact role of circulating HSP70 in the development of atherosclerosis is still limited. In the present study, we report an adhesion-promoting effect of exogenous HSP70 and evaluate the potential involvement of elevated circulating HSP70 in the development of atherosclerosis. Time-dependent elevation of plasma HSP70 was found in diet-induced atherosclerotic rats, whose effect was investigated through further in vitro experiments. In rat aortic endothelial cell (RAEC) cultures, exogenous HSP70 incubation neither produced cell injuries by itself nor had protective effects on cell injuries caused by Ox-LDL or homocysteine. However, exogenous HSP70 administration could lead to a higher adhesion rate between rat peripheral blood monocytes (PBMCs) and RAECs. This adhesion-promoting effect appeared only when PBMCs, rather than RAECs, were pretreated with HSP70 incubation. PBMCs in an HSP70 environment released more IL-6 to supernatant, which subsequently up-regulated the expression of ICAM-1 in RAECs. These results indicate that the diet-induced elevation of circulating HSP70 could trigger cell adhesion with the help of IL-6 as a mediator, which provides a novel possible mechanism for understanding the role of circulating HSP70 in the pathogenesis of atherosclerosis.
authors.affiliation: Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping Road, Haidian, Beijing, 100039, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping Road, Haidian, Beijing, 100039, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhan
authors.affiliation: Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping Road, Haidian, Beijing, 100039, People's Republic of China.
authors.forename: Li-Cheng
authors.initials: LC
authors.lastname: Yan
authors.affiliation: Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping Road, Haidian, Beijing, 100039, People's Republic of China.
authors.forename: Jing-Bo
authors.initials: JB
authors.lastname: Gong
authors.affiliation: Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping Road, Haidian, Beijing, 100039, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping Road, Haidian, Beijing, 100039, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Stress Medicine, Institute of Basic Medical Sciences, #27 Taiping Road, Haidian, Beijing, 100039, People's Republic of China. newjia@vip.sina.com.
authors.forename: Ling-Jia
authors.initials: LJ
authors.lastname: Qian
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood* / Q000209:etiology; D002448:Cell Adhesion; D002470:Cell Survival; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects*; D042783:Endothelial Cells / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000097:blood*; D015850:Interleukin-6 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D009000:Monocytes / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D018840:HSP70 Heat-Shock Proteins; D015850:Interleukin-6; D008077:Lipoproteins, LDL
keywords: Atherosclerosis; Cell adhesion; Circulating HSP70; Exogenous HSP70; IL-6