Krüppel-like factor 14 inhibits atherosclerosis via mir-27a-mediated down-regulation of lipoprotein lipase expression in vivo
Authors: Chao-Ke Tang
Yun-Cheng Lv
Min Zhang
Xiao-Yan Dai
Wei Xie
Da-Wei Zhang
Zhen-Wang Zhao
Liang Li
Wei-Dong Yin
Xi-Long Zheng
Duo Gong
Dong-Ming Guo
Journal: Atherosclerosis (2019)
Discipline: CLINICAL MEDICINE
Keywords: Atherosclerosis; Inflammation; Krüppel-like factor; Lipoprotein lipase; Macrophage
Affiliations: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, Hunan, China; Clinical Anatomy & Reproductive Medicine Application Institute, University of South China, Hengyang, 421001, Hunan, China., Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, Hunan, China; Department of Pathophysiology, University of South China, Hengyang, 421001, Hunan, China., Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, Hunan, China., Clinical Anatomy & Reproductive Medicine Application Institute, University of South China, Hengyang, 421001, Hunan, China., Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, The University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta, Canada, T2N 4N1; Key Laboratory of Molecular Targets & Clinical Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, 511436, China., Department of Pediatrics and Group on the Molecular and Cell Biology of Lipids, University of Alberta, Alberta, Canada., Guangdong Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 511436, China., Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, Hunan, China. Electronic address: .

Abstract:  Background and aims: 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. Methods and results: 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. Conclusions: KLF14 plays an antiatherogenic role via the miR-27a-dependent down-regulation of LPL and subsequent inhibition of proinflammatory cytokine secretion and lipid accumulation. 

Retracted: No

PubPeer comments:
 Figure 3I. The same bar graph is repeated 3 times in the same subfigure. This paper is part of a growing number of papers by the same senior author on topics related to lipid metabolism and atherosclerosis that contain questionable data and images. ![file] ,