Cytosolic Hsp60 orchestrates the survival and inflammatory responses of vascular smooth muscle cells in injured aortic vessels
- 주제(키워드) Hsp60 , Inflammation , NF-κB , Restenosis , Vascular smooth muscle cells
- 등재 SCIE, SCOPUS
- 발행기관 Oxford University Press
- 발행년도 2015
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000115941
- 본문언어 영어
- Published As http://dx.doi.org/10.1093/cvr/cvv130
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Aims: 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. Methods and results: 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. Conclusions: 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. © 2015 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015.
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