Fibronectin type III domain containing 5 attenuates NLRP3 inflammasome activation and phenotypic transformation of adventitial fibroblasts in spontaneously hypertensive rats.

Abstract:

OBJECTIVE:Phenotypic transformation of adventitial fibroblasts is important in the pathogenesis of hypertension. This study was designed to determine whether fibronectin type III domain containing 5 (FNDC5) alleviates the phenotypic transformation of adventitial fibroblasts in hypertension and the underlying mechanisms. METHODS AND RESULTS:Experiments were carried out in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and primary aortic adventitial fibroblasts. FNDC5 was downregulated and NLRP3 inflammasome was activated in aortic adventitia of SHR. FNDC5 overexpression attenuated adventitial fibroblasts phenotypic transformation, excessive synthesis and secretion of matrix components, NLRP3 inflammasome activation and inflammation in adventitial fibroblasts from SHR. Moreover, FNDC5 overexpression reduced NADPH oxidase 2 (NOX2) expression and reactive oxygen species (ROS) production in adventitial fibroblasts from SHR. Similarly, exogenous FNDC5 inhibited adventitial fibroblasts phenotypic transformation, expression of matrix components, NLRP3 inflammasome activation and NOX2 expression in adventitial fibroblasts from SHR. FNDC5 overexpression in rats attenuated phenotypic transformation, inflammation and reactive oxygen species (ROS) production in the aortic adventitia of SHR. Furthermore, FNDC5 overexpression reduced blood pressure and alleviated vascular remodeling in SHR. CONCLUSION:FNDC5 reduces NOX2-derived ROS production, NLRP3 inflammasome activation and phenotypic transformation in adventitial fibroblasts of SHR. FNDC5 plays a beneficial role in attenuating vascular inflammation, vascular remodeling and hypertension in SHR.

journal_name

J Hypertens

journal_title

Journal of hypertension

authors

Ling L,Chen D,Tong Y,Zang YH,Ren XS,Zhou H,Qi XH,Chen Q,Li YH,Kang YM,Zhu GQ

doi

10.1097/HJH.0000000000001654

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

1104-1114

issue

5

eissn

0263-6352

issn

1473-5598

journal_volume

36

pub_type

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