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Biochem Biophys Res Commun. 2017 Aug 19;490(2):580-586. doi: 10.1016/j.bbrc.2017.06.081. Epub 2017 Jun 15.

C1q/TNF-related protein 1 promotes endothelial barrier dysfunction under disturbed flow.

Author information

1
Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Institute of Cardiovascular Diseases, Shanghai Jiao Tong University, Shanghai, PR China.
2
Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
3
Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Institute of Cardiovascular Diseases, Shanghai Jiao Tong University, Shanghai, PR China. Electronic address: Xiaoqun_Wang@hotmail.com.
4
Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Institute of Cardiovascular Diseases, Shanghai Jiao Tong University, Shanghai, PR China. Electronic address: rjlulin1965@163.com.

Abstract

Endothelial hyper-permeability is a major determinant factor that contributes to the accelerated development of atherosclerotic lesions at hemodynamically disturbed sites. Previously, we showed that C1q/TNF related protein (CTRP) 1 promotes endothelium-leukocyte interactions and inflammatory responses in vascular cells. Here, we sought to investigate the role of CTRP1 in modulation of endothelial permeability under disturbed flow condition. By using en face staining of mouse aorta, we found CTRP1 expression was significantly increased in vascular endothelial cells under disturbed flow as compared to steady laminar flow. Vascular permeability to Evans blue dye was notably enhanced in CTRP1 knockin mice as compared to wild type animals, whereas aortic hyper-permeability at disturbed sites was remarkably restored after deletion of CTRP1. In cultured endothelial cells, treatment of CTRP1 led to increased permeability to fluorescent-labelled dextran and apparent formation of paracellular holes as observed after disturbed flow exposure, which was evidently reduced in the presence of a CTRP1-specific neutralizing antibody. Mechanistically, we found activation of VEGFR2 by CTRP1 might be involved in vascular hyper-permeability under disturbed flow condition. Taken together, this study suggests that CTRP1 is a mechano-sensitive proinflammatory factor that mediates disturbed flow-induced vascular barrier dysfunction. Inhibition of CTRP1 may inhibit the pathogenesis of atherosclerosis at early stage.

KEYWORDS:

CTRP1; Disturbed flow; Endothelial cell; Permeability

PMID:
28625919
DOI:
10.1016/j.bbrc.2017.06.081
[Indexed for MEDLINE]

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