Heat shock protein 70 is secreted from endothelial cells by a non-classical pathway involving exosomes.
Emerging evidence suggests that a high level of circulating heat shock protein 70 (HSP70) correlates with a lower risk of vascular disease; however, the biological significance of this inverse relationship has not been explored. Herein, we report that oxidative low density lipoprotein (Ox-LDL) and homocysteine (Hcy) induce HSP70 release from endothelial cells. In rat endothelial cells, Ox-LDL and Hcy induced robust release of HSP70, independent of the classical route of endoplasmic reticulum/Golgi protein trafficking or the formation of lipid rafts. In contrast, Ox-LDL and Hcy significantly enhanced the exosomal secretory rate and increased the HSP70 content of exosomes. Exogenous HSP70 had no impact on LPS-, Ox-LDL- and Hcy-induced activation of endothelial cells, whereas HSP70 did activate monocytes alone, resulting in monocyte adhesion to endothelial cells. These results indicate that exosome-dependent secretion of HSP70 from endothelial cells provides a novel paracrine mechanism to regulate vascular endothelial functional integrity.
Zhan
Rui
R
Department of Stress Medicine, Institute of Health & Environmental Medicine, Tianjin 300050, China.
Leng
Xue
X
Liu
Xiaohua
X
Wang
Xinxing
X
Gong
Jingbo
J
Yan
Licheng
L
Wang
Liqun
L
Wang
Yang
Y
Wang
Xiaoming
X
Qian
Ling-Jia
LJ
D000818:Animals; D054885:Cumulus Cells; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D055354:Exosomes / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D051381:Rats
D018840:HSP70 Heat-Shock Proteins