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Krüppel-like factor 14 inhibits atherosclerosis via mir-27a-mediated down-regulation of lipoprotein lipase expression in vivo.

Authors :
Xie, Wei
Li, Liang
Gong, Duo
Zhang, Min
Lv, Yun-Cheng
Guo, Dong-ming
Zhao, Zhen-Wang
Zheng, Xi-Long
Zhang, Da-Wei
Dai, Xiao-Yan
Yin, Wei-Dong
Tang, Chao-Ke
Source :
Atherosclerosis (00219150). Oct2019, Vol. 289, p143-161. 19p.
Publication Year :
2019

Abstract

Krüppel-like factor 14 (KLF14) is known to play a role in atherosclerosis, but the underlying mechanisms are still largely unknown. The aim of our study was to explore the effects of KLF14 on lipid metabolism and inflammatory response, providing a potential target for lowering the risk of atherosclerosis-causing disease. mRNA and protein levels of KLF14 were significantly decreased in oxidized low-density lipoprotein (oxLDL)-treated macrophages and in the atherosclerotic lesion area. Chromatin immunoprecipitation (ChIP) and luciferase reporter gene assays were used to confirm that KLF14 positively regulated miR-27a expression by binding to its promoter. We also found that KLF14 could restored appropriate cellular lipid homeostasis and inflammatory responses via negatively regulating lipoprotein lipase (LPL) expression in THP1-derived macrophages through miR-27a. In addition, gypenosides (GP), a KLF14 activator, delayed the development of atherosclerosis in apolipoprotein E deficient (apoE −/− ) mice. KLF14 plays an antiatherogenic role via the miR-27a-dependent down-regulation of LPL and subsequent inhibition of proinflammatory cytokine secretion and lipid accumulation. Image 1 • KLF14 inhibits proinflammatory cytokines and lipid accumulation in macrophages via binding to the promoter of miR-27a. • MiR-27a-mediated LPL downregulation participates in the inhibitory effect of KLF14 on inflammation and lipid accumulation. • Gypenosides, a KLF14 activator, delays the development of atherosclerosis in apoE −/− mice. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00219150
Volume :
289
Database :
Academic Search Index
Journal :
Atherosclerosis (00219150)
Publication Type :
Academic Journal
Accession number :
139029732
Full Text :
https://doi.org/10.1016/j.atherosclerosis.2019.08.012