MicroRNA-19b promotes macrophage cholesterol accumulation and aortic atherosclerosis by targeting ATP-binding cassette transporter A1
Authors: Chao-Ke Tang
Yun-Cheng Lv
Min Zhang
Wei Xie
Juan Peng
Da-Wei Zhang
Jing Yang
Dan Liu
Yan-Yan Tang
Deng-Pei Tang
Feng Yao
Ping-Ping He
Yu-Lin Tan
Xin-Ping Ouyang
Guo-Jun Zhao
Guo-Ping Tian
Xi-Long Zheng
Francisco S Cayabyab
Journal: Atherosclerosis (2014)
Discipline: CLINICAL MEDICINE
Keywords: ABCA1; Atherosclerosis; Cholesterol accumulation; Macrophage; miR-19b.
Affiliations: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang 421001, Hunan, China; Laboratory of Clinical Anatomy, University of South China, Hengyang 421001, China., Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang 421001, Hunan, China., Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang 421001, Hunan, China; Clinical Medical Research Institute of the First Affiliated Hospital, University of South China, Hengyang 421001, China., Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada., Department of Physiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada., Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, The University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1, Canada., Department of Pediatrics and Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada., Department of Cardiovascular Medicine, Second Affiliated Hospital of University of South China, Hengyang 421001, Hunan, China. Electronic address: ., Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang 421001, Hunan, China. Electronic address: .

Abstract:  Rationale: Macrophage accumulation of cholesterol leads to foam cell formation which is a major pathological event of atherosclerosis. Recent studies have shown that microRNA (miR)-19b might play an important role in cholesterol metabolism and atherosclerotic diseases. Here, we have identified miR-19b binding to the 3'UTR of ATP-binding cassette transporter A1 (ABCA1) transporters, and further determined the potential roles of this novel interaction in atherogenesis. Objective: To investigate the molecular mechanisms involved in a miR-19b promotion of macrophage cholesterol accumulation and the development of aortic atherosclerosis. Methods and results: We performed bioinformatics analysis using online websites, and found that miR-19b was highly conserved during evolution and directly bound to ABCA1 mRNA with very low binding free energy. Luciferase reporter assay confirmed that miR-19b bound to 3110-3116 sites within ABCA1 3'UTR. MiR-19b directly regulated the expression levels of endogenous ABCA1 in foam cells derived from human THP-1 macrophages and mouse peritoneal macrophages (MPMs) as determined by qRT-PCR and western blot. Cholesterol transport assays revealed that miR-19b dramatically suppressed apolipoprotein AI-mediated ABCA1-dependent cholesterol efflux, resulting in the increased levels of total cholesterol (TC), free cholesterol (FC) and cholesterol ester (CE) as revealed by HPLC. The excretion of (3)H-cholesterol originating from cholesterol-laden MPMs into feces was decreased in mice overexpressing miR-19b. Finally, we evaluated the proatherosclerotic role of miR-19b in apolipoprotein E deficient (apoE(-/-)) mice. Treatment with miR-19b precursor reduced plasma high-density lipoprotein (HDL) levels, but increased plasma low-density lipoprotein (LDL) levels. Consistently, miR-19b precursor treatment increased aortic plaque size and lipid content, but reduced collagen content and ABCA1 expression. In contrast, treatment with the inhibitory miR-19b antisense oligonucleotides (ASO) prevented or reversed these effects. Conclusion: MiR-19b promotes macrophage cholesterol accumulation, foam cell formation and aortic atherosclerotic development by targeting ABCA1. 

Retracted: No

PubPeer comments:
 Figures 2 and 3. This doesn t look too good. 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] , 
 Figure 2. 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. Besides manipulations with Western blot images, across these papers, there is a pattern of bar graphs that look too similar but aren t 100% identical. Here is just an example. ![file] , 
 Copy pasted from https: doi.org 10.1016 j.atherosclerosis.2021.06.920 :  Editorial expression of concern: u201cMicroRNA-19b promotes macrophage cholesterol accumulation and aortic atherosclerosis by targeting ATP-binding cassette transporter A1u201d [Atherosclerosis Volume 236, Issue 1, September 2014, Pages 215u2013226]. Published:June 28, 2021. The Editors of Atherosclerosis are issuing an expression of concern to alert readers that credible concerns have been raised regarding the quality of some data in the article above. See also https: retractionwatch.com 2021 07 09 they-seem-to-mean-business-cardiology-journal-flags-papers-cited-hundreds-of-times ,