title: Cytosolic Hsp60 orchestrates the survival and inflammatory responses of vascular smooth muscle cells in injured aortic vessels.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Department of Life Science and Ewha Research Center for Systems Biology, Ewha Womans University, Seoul 127-750, Korea The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750, Korea.
authors: Boae
authors: B
authors: Choi
authors: Department of Life Science and Ewha Research Center for Systems Biology, Ewha Womans University, Seoul 127-750, Korea The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750, Korea.
authors: Mina
authors: M
authors: Choi
authors: Department of Life Science and Ewha Research Center for Systems Biology, Ewha Womans University, Seoul 127-750, Korea.
authors: Charny
authors: C
authors: Park
authors: Department of Life Science and Ewha Research Center for Systems Biology, Ewha Womans University, Seoul 127-750, Korea The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750, Korea.
authors: Eun Kyung
authors: EK
authors: Lee
authors: Department of Life Science and Ewha Research Center for Systems Biology, Ewha Womans University, Seoul 127-750, Korea The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750, Korea.
authors: Dong Hoon
authors: DH
authors: Kang
authors: Department of Life Science and Ewha Research Center for Systems Biology, Ewha Womans University, Seoul 127-750, Korea The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750, Korea.
authors: Doo Jae
authors: DJ
authors: Lee
authors: Department of Life Science and Ewha Research Center for Systems Biology, Ewha Womans University, Seoul 127-750, Korea The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750, Korea.
authors: Jae Yoon
authors: JY
authors: Yeom
authors: Department of Life Science and Ewha Research Center for Systems Biology, Ewha Womans University, Seoul 127-750, Korea.
authors: Yeonjoo
authors: Y
authors: Jung
authors: Department of Life Science and Ewha Research Center for Systems Biology, Ewha Womans University, Seoul 127-750, Korea.
authors: Jaesang
authors: J
authors: Kim
authors: Department of Life Science and Ewha Research Center for Systems Biology, Ewha Womans University, Seoul 127-750, Korea sanghyuk@ewha.ac.kr kangsw@ewha.ac.kr.
authors: Sanghyuk
authors: S
authors: Lee
authors: Department of Life Science and Ewha Research Center for Systems Biology, Ewha Womans University, Seoul 127-750, Korea The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750, Korea sanghyuk@ewha.ac.kr kangsw@ewha.ac.kr.
authors: Sang Won
authors: SW
authors: Kang
mesh_terms: D000818:Animals; D001011:Aorta / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D001025:Aortitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D058426:Neointima; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D066253:Vascular Remodeling; D057772:Vascular System Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D018834:Chaperonin 60; C060293:HSPD1 protein, human; C557067:Hspd1 protein, rat; D018836:Inflammation Mediators; D024101:Mitochondrial Proteins; D016328:NF-kappa B; D009841:Oligonucleotides; D051550:I-kappa B Kinase
keywords: Hsp60; Inflammation; NF-κB; Restenosis; Vascular smooth muscle cells