Effects of miR-33a-5P on ABCA1/G1-mediated cholesterol efflux under inflammatory stress in THP-1 macrophages
Authors: Suxin Luo
Quan He
Zhong Zuo
Qing Li
Xiong Z Ruan
Nan Zhang
Min Mao
Chao Zhou
Han Lei
Yaxi Chen
Lei Zhao
Qing Liu
Wei Huang
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: inflammatory cytokines; ABCA1; ABCG1; miR-33a-5P; cholesterol efflux
Affiliations: Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China; Centre for Lipid Research, Key Laboratory of Metabolism on Lipid and Glucose, Chongqing Medical University, Chongqing, P.R. China; Centre for Clinical Research, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China., Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China; Centre for Lipid Research, Key Laboratory of Metabolism on Lipid and Glucose, Chongqing Medical University, Chongqing, P.R. China., Centre for Clinical Research, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China., Centre for Lipid Research, Key Laboratory of Metabolism on Lipid and Glucose, Chongqing Medical University, Chongqing, P.R. China., Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China., Centre for Lipid Research, Key Laboratory of Metabolism on Lipid and Glucose, Chongqing Medical University, Chongqing, P.R. China; John Moorhead Research Laboratory, Centre for Nephrology, University College London Medical School, Royal Free Campus, London, United Kingdom.

Abstract:  The present study is to investigate whether inflammatory cytokines inhibit ABCA1/ABCG1-mediated cholesterol efflux by regulating miR-33a-5P in THP-1 macrophages. We used interleukin-6 and tumor necrosis factor-alpha in the presence or absence of native low density lipoprotein (LDL) to stimulate THP-1 macrophages. THP-1 macrophages were infected by either control lentivirus vectors or lentivirus encoding miR-33a-5P or antisense miR-33a-5P. The effects of inflammatory cytokines, miR-33a-5P and antisense miR-33a-5P on intracellular lipids accumulation and intracellular cholesterol contents were assessed by oil red O staining and quantitative intracellular cholesterol assay. ApoA-I-mediated cholesterol efflux was examined using the fluorescent sterol (BODIPY-cholesterol). The gene and protein expressions of the molecules involved in cholesterol trafficking were examined using quantitative real-time polymerase chain reaction and Western blotting. Inflammatory cytokines or miR-33a-5P increased intracellular lipid accumulation and decreased apoA-I-mediated cholesterol efflux via decreasing the expression of ABCA1 and ABCG1 in the absence or presence of LDL in THP-1 macrophages. However, antisense miR-33a-5P reversed the effects of inflammatory cytokines on intracellular lipid accumulation, cholesterol efflux, and the expression of miR-33a-5P, ABCA1 and ABCG1 in the absence or presence of LDL in THP-1 macrophages. This study indicated that inflammatory cytokines inhibited ABCA1/ABCG1-mediated cholesterol efflux by up-regulating miR-33a-5P in THP-1 macrophages. 

Retracted: No

PubPeer comments:
 Figure 1A appears to have two images which overlap but are described differently. The coloring is slightly different. *** ![file] , 
 I agree with #1 and have an additional concern about Figure 1A and 3A: * Yellow boxes: Two panels might appear to show an overlap ![file] , 
 Figure 4: * Cyan boxes: Two panels appear to show an overlap ![file] ,