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Coxsackievirus and adenovirus receptor mediates the responses of endothelial cells to fluid shear stress

  • 주제(기타) Biochemistry & Molecular Biology; Medicine, Research & Experimental
  • 설명문(일반) [Chung, Jihwa; Kim, Kyoung Hwa; An, Shung Hyun; Kwon, Kihwan] Ewha Womans Univ, Med Res Inst, Sch Med, Seoul 07985, South Korea; [Lee, Sunmi; Kang, Sang Won] Ewha Womans Univ, Dept Life Sci, Coll Nat Sci, Seoul 03760, South Korea; [Lim, Byung-Kwan] Jungwon Univ, Dept Biomed Sci, Goesan Gun 28024, Chungbuk, South Korea; [Kwon, Kihwan] Ewha Womans Univ, Sch Med, Div Cardiol, Dept Internal Med, Seoul 07985, South Korea
  • 등재 SCIE, SCOPUS, KCI등재
  • OA유형 Green Published, gold
  • 발행기관 NATURE PUBLISHING GROUP
  • 발행년도 2019
  • 총서유형 Journal
  • URI http://www.dcollection.net/handler/ewha/000000165887
  • 본문언어 영어
  • Published As http://dx.doi.org/10.1038/s12276-019-0347-7
  • PubMed https://pubmed.ncbi.nlm.nih.gov/31776326

초록/요약

Endothelial mechanotransduction by fluid shear stress (FSS) modulates endothelial function and vascular pathophysiology through mechanosensors on the cell membrane. The coxsackievirus and adenovirus receptor (CAR) is not only a viral receptor but also a component of tight junctions and plays an important role in tissue homeostasis. Here, we demonstrate the expression, regulatory mechanism, and role of CAR in vascular endothelial cells (ECs) under FSS conditions. Disturbed flow increased, whereas unidirectional laminar shear stress (LSS) decreased, CAR expression in ECs through the Kruppel-like factor 2 (KLF2)/activator protein 1 (AP-1) axis. Deletion of CAR reduced the expression of proinflammatory genes and endothelial inflammation induced by disturbed flow via the suppression of NE-kappa B activation. Consistently, disturbed flow-induced atherosclerosis was reduced in EC-specific CAR KO mice. CAR was found to be involved in endothelial mechanotransduction through the regulation of platelet endothelial cell adhesion molecule 1 (PECAM-1) phosphorylation. Our results demonstrate that endothelial CAR is regulated by FSS and that this regulated CAR acts as an important modulator of endothelial mechanotransduction by FSS.

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