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Cardiovascular research

Cytosolic Hsp60 orchestrates the survival and inflammatory responses of vascular smooth muscle cells in injured aortic vessels.


PMID 25870185

Abstract

Pro-inflammatory response of vascular smooth muscle cells (VSMCs) is triggered by endothelial damage and a causative step for thrombosis and neointimal thickening in the injured arterial vessels. Therefore, we investigate a role of cytosolic Hsp60 as a novel pro-inflammatory mediator in VSMCs. Hsp60 was detected in the cytosol of VSMCs. The selective depletion of cytosolic Hsp60 in VSMCs reduced the IκB kinase activation, repressed the induction of nuclear factor (NF)-κB-dependent survival genes (MnSOD and Bfl-1/A1), and enhanced apoptotic death in response to TNF-α. Moreover, a quantitative RNA sequencing revealed that the expression of 75 genes among the 774 TNF-α-inducible genes was significantly reduced by the depletion of cytosolic Hsp60. In particular, the expression of pro-inflammatory cytokines/chemokines, such as CCL2, CCL20, and IL-6, was regulated by the cytosolic Hsp60 in VSMCs. Finally, the depletion of cytosolic Hsp60 markedly inhibited the neointimal thickening in the balloon-injured arterial vessels by inducing apoptotic cell death and inhibiting chemokine production. This study provides the first evidence that cytosolic Hsp60 could be a therapeutic target for preventing VSMC hyperplasia and inflammatory response in the injured vessels.