Ablation of miR-144 increases vimentin expression and atherosclerotic plaque formation

• Published in: Scientific reports Vol. 10; no. 1; p. 6127
• Main Authors: He, Quan, Wang, Fangfei, Honda, Takashi, Greis, Kenneth D., Redington, Andrew N.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.04.2020; Nature Publishing Group
• Subjects: 692/308/1426; 692/4019/592; Animals; Aorta; Arteriosclerosis; Atherosclerosis; Cell culture; Cells, Cultured; Cholesterol; Diet; Endothelial cells; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Fatty liver; High fat diet; Humanities and Social Sciences; Liquid chromatography; Liver diseases; Male; Mass spectrometry; Mass spectroscopy; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; MicroRNAs - metabolism; multidisciplinary; Plaque, Atherosclerotic - genetics; Plaque, Atherosclerotic - metabolism; Rodents; Science; Science (multidisciplinary); Trypsin; Vimentin; Vimentin - genetics; Vimentin - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-63335-7

It has been suggested that miR-144 is pro-atherosclerotic via effects on reverse cholesterol transportation targeting the ATP binding cassette protein. This study used proteomic analysis to identify additional cardiovascular targets of miR-144, and subsequently examined the role of a newly identified regulator of atherosclerotic burden in miR-144 knockout mice receiving a high fat diet. To identify affected secretory proteins, miR-144 treated endothelial cell culture medium was subjected to proteomic analysis including two-dimensional gel separation, trypsin digestion, and nanospray liquid chromatography coupled to tandem mass spectrometry. We identified 5 gel spots representing 19 proteins that changed consistently across the biological replicates. One of these spots, was identified as vimentin. Atherosclerosis was induced in miR-144 knockout mice by high fat diet and vascular lesions were quantified by Oil Red-O staining of the serial sectioned aortic root and from en-face views of the aortic tree. Unexpectedly, high fat diet induced extensive atherosclerosis in miR-144 knockout mice and was accompanied by severe fatty liver disease compared with wild type littermates. Vimentin levels were reduced by miR-144 and increased by antagomiR-144 in cultured cardiac endothelial cells. Compared with wild type, ablation of the miR-144/451 cluster increased plasma vimentin, while vimentin levels were decreased in control mice injected with synthetic miR-144. Furthermore, increased vimentin expression was prominent in the commissural regions of the aortic root which are highly susceptible to atherosclerotic plaque formation. We conclude that miR-144 maybe a potential regulator of the development of atherosclerosis via changes in vimentin signaling.