Abstract
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.
Original language | English |
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Pages (from-to) | 498-508 |
Number of pages | 11 |
Journal | Cardiovascular Research |
Volume | 106 |
Issue number | 3 |
DOIs | |
State | Published - 1 Jun 2015 |
Bibliographical note
Publisher Copyright:© 2015 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015.
Keywords
- Hsp60
- Inflammation
- NF-κB
- Restenosis
- Vascular smooth muscle cells