Diosgenin inhibits atherosclerosis via suppressing the MiR-19b-induced downregulation of ATP-binding cassette transporter A1
Authors: Xin-ping Ouyang
Chao-ke Tang
Feng Yao
Min Zhang
Ping-ping He
Wei Xie
Yu-lin Tan
Jing Yang
Yun-cheng Lv
Liang Li
Xi-Long Zheng
Francisco S Cayabyab
Yan-yan Tang
Dan Liu
Journal: Atherosclerosis (2015)
Discipline: CLINICAL MEDICINE
Keywords: ABCA1; Atherosclerosis; Cholesterol efflux; Diosgenin; Macrophage foam cells
Affiliations: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China; Laboratory of Clinical Anatomy, University of South China, Hengyang 421001, China., Department of Metabolism & Endocrinology of the First Affiliated Hospital, University of South China, Hengyang 421001, China., Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China; Department of Laboratory Animal Science, University of South China, Hengyang 421001, China., Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China., Department of Surgery, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada., Department of Biochemistry and Molecular Biology, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1, Canada., Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China. Electronic address: .

Abstract:  Rationale: Diosgenin (Dgn), a structural analogue of cholesterol, has been reported to have the hypolipidemic and antiatherogenic properties, but the underlying mechanisms are not fully understood. Given the key roles of macrophages in cholesterol metabolism and atherogenesis, it is critical to investigate macrophage cholesterol efflux and development of atherosclerotic lesion after Dgn treatment. Objective: This study was designed to evaluate the potential effects of Dgn on macrophage cholesterol metabolism and the development of aortic atherosclerosis, and to explore its underlying mechanisms. Methods and results: Dgn significantly up-regulated the expression of ATP-binding cassette transporter A1 (ABCA1) protein, but didn't affect liver X receptor α levels in foam cells derived from human THP-1 macrophages and mouse peritoneal macrophages (MPMs) as determined by western blotting. The miR-19b levels were markedly down-regulated in Dgn-treated THP-1 macrophages/MPM-derived foam cells. Cholesterol transport assays revealed that treatment with Dgn alone or together with miR-19b inhibitor notably enhanced ABCA1-dependent cholesterol efflux, resulting in the reduced levels of total cholesterol, free cholesterol and cholesterol ester as determined by high-performance liquid chromatography. The fecal 3H-sterol originating from cholesterol-laden MPMs was increased in apolipoprotein E knockout mice treated with Dgn or both Dgn and antagomiR-19b. Treatment with Dgn alone or together with antagomiR-19b elevated plasma high-density lipoprotein levels, but reduced plasma low-density lipoprotein levels. Accordingly, aortic lipid deposition and plaque area were reduced, and collagen content and ABCA1 expression were increased in mice treated with Dgn alone or together with antagomiR-19b. However, miR-19b overexpression abrogated the lipid-lowering and atheroprotective effects induced by Dgn. Conclusion: The present study demonstrates that Dgn enhances ABCA1-dependent cholesterol efflux and inhibits aortic atherosclerosis progression by suppressing macrophage miR-19b expression. 

Retracted: No

PubPeer comments:
 Copy pasted from https: doi.org 10.1016 j.atherosclerosis.2021.06.921 :  Editorial Expression of Concern: u201cDiosgenin inhibits atherosclerosis via suppressing the MiR-19b-induced downregulation of ATP-binding cassette transporter A1u201d [Atherosclerosis Volume 240, Issue 1, May 2015, Pages 80u201389]. Published:June 25, 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 ,