Luiza B C T Coimbra, Andrea Pinto-Martinez, Isadora C B Pavan, Everton G Melo, Thaís L S Araujo
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引用次数: 0
Abstract
Heat shock proteins (HSPs) play crucial roles in human endothelial cell functions such as migration and angiogenesis. However, human heat shock protein dynamics under stress conditions such as heat shock and hypoxia in human endothelial cells (ECs) are enigmatic, and the characteristics of HSPs in endothelial cells after exposure to thermal stress and a low-oxygen environment are unknown. We hypothesized that endothelial cells (ECs) adapt to heat shock (HS) and hypoxia by modulating chaperome oligomerization and that HSP70 is a major determinant of the endothelial phenotype. HSP70 inhibition with VER-155008 or YM-1 in primary human endothelial cells decreases EC proliferation, migration and angiogenesis at baseline and after heat shock recovery. We showed that vascular-independent HSC/P70 multimeric complexes in primary human veins (HUVECs) and coronary artery ECs (HCAECs) accumulate after HS and are decreased by hypoxia. Heat shock recovery increases the number of HSP90 dimers, inducible HSP70, and HSP40 macromolecular complexes, whereas HSC70 returns to baseline. We demonstrated that the heat shock response and hypoxia regulate HSPs through a new layer of complexity, oligomerization, in addition to classical cochaperone/NEF interactions. The biphasic temporal oligomerization of molecular chaperones in the recovery phase provides a novel face of the heat shock response. In addition, shifts in the subcellular location and upregulation of HSP70 were also observed here. The decrease in HSP expression caused by hypoxia raises the possibility that decreased chaperone power contributes to the endothelial dysfunction found in atherosclerosis, thrombosis and cancer. Together, these results show that HSP70 is pivotal to the healthy endothelial response in veins and coronary arteries, and we revealed human HSP dynamics in the vascular response to proteotoxic stress.
期刊介绍:
Cell Stress and Chaperones is an integrative journal that bridges the gap between laboratory model systems and natural populations. The journal captures the eclectic spirit of the cellular stress response field in a single, concentrated source of current information. Major emphasis is placed on the effects of climate change on individual species in the natural environment and their capacity to adapt. This emphasis expands our focus on stress biology and medicine by linking climate change effects to research on cellular stress responses of animals, micro-organisms and plants.