The miR-378c-Samd1 circuit promotes phenotypic modulation of vascular smooth muscle cells and foam cells formation in atherosclerosis lesions

Abstract MicroRNAs have emerged as key regulators in vascular diseases and are involved in the formation of atherosclerotic lesions. However, the atherosclerotic-specific MicroRNAs and their functional roles in atherosclerosis are unclear. Here, we report that miR-378c protects against atheroscleros...

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Autores principales:	Shengya Tian, Yang Cao, Jinliang Wang, Yongjun Bi, Jingquan Zhong, Xiangbin Meng, Wenyu Sun, Ruixue Yang, Luping Gan, Xuping Wang, Hongshi Li, Rong Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/71186c3423784ba784512adbea8a5402
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spelling	oai:doaj.org-article:71186c3423784ba784512adbea8a54022021-12-02T16:51:26ZThe miR-378c-Samd1 circuit promotes phenotypic modulation of vascular smooth muscle cells and foam cells formation in atherosclerosis lesions10.1038/s41598-021-89981-z2045-2322https://doaj.org/article/71186c3423784ba784512adbea8a54022021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89981-zhttps://doaj.org/toc/2045-2322Abstract MicroRNAs have emerged as key regulators in vascular diseases and are involved in the formation of atherosclerotic lesions. However, the atherosclerotic-specific MicroRNAs and their functional roles in atherosclerosis are unclear. Here, we report that miR-378c protects against atherosclerosis by directly targeting Sterile Alpha Motif Domain Containing 1 (Samd1), a predicted transcriptional repressor. miR-378c was strikingly reduced in atherosclerotic plaques and blood of acute coronary syndrome (ACS) patients relative to healthy controls. Suppression of miR-378c promoted vascular smooth muscle cells (VSMCs) phenotypic transition during atherosclerosis. We also reported for the first time that Samd1 prolonged immobilization of LDL on the VSMCs, thus facilitated LDL oxidation and subsequently foam cell formation. Further, we found that Samd1 contains predicted DNA binding domain and directly binds to DNA regions as a transcriptional repressor. Together, we uncovered a novel mechanism whereby miR-378c-Samd1 circuit participates in two key elements of atherosclerosis, VSMCs phenotypic transition and LDL oxidation. Our results provided a better understanding of atherosclerosis pathophysiology and potential therapeutic management by targeting miR-378c-Samd1 circuit.Shengya TianYang CaoJinliang WangYongjun BiJingquan ZhongXiangbin MengWenyu SunRuixue YangLuping GanXuping WangHongshi LiRong WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shengya Tian Yang Cao Jinliang Wang Yongjun Bi Jingquan Zhong Xiangbin Meng Wenyu Sun Ruixue Yang Luping Gan Xuping Wang Hongshi Li Rong Wang The miR-378c-Samd1 circuit promotes phenotypic modulation of vascular smooth muscle cells and foam cells formation in atherosclerosis lesions
description	Abstract MicroRNAs have emerged as key regulators in vascular diseases and are involved in the formation of atherosclerotic lesions. However, the atherosclerotic-specific MicroRNAs and their functional roles in atherosclerosis are unclear. Here, we report that miR-378c protects against atherosclerosis by directly targeting Sterile Alpha Motif Domain Containing 1 (Samd1), a predicted transcriptional repressor. miR-378c was strikingly reduced in atherosclerotic plaques and blood of acute coronary syndrome (ACS) patients relative to healthy controls. Suppression of miR-378c promoted vascular smooth muscle cells (VSMCs) phenotypic transition during atherosclerosis. We also reported for the first time that Samd1 prolonged immobilization of LDL on the VSMCs, thus facilitated LDL oxidation and subsequently foam cell formation. Further, we found that Samd1 contains predicted DNA binding domain and directly binds to DNA regions as a transcriptional repressor. Together, we uncovered a novel mechanism whereby miR-378c-Samd1 circuit participates in two key elements of atherosclerosis, VSMCs phenotypic transition and LDL oxidation. Our results provided a better understanding of atherosclerosis pathophysiology and potential therapeutic management by targeting miR-378c-Samd1 circuit.
format	article
author	Shengya Tian Yang Cao Jinliang Wang Yongjun Bi Jingquan Zhong Xiangbin Meng Wenyu Sun Ruixue Yang Luping Gan Xuping Wang Hongshi Li Rong Wang
author_facet	Shengya Tian Yang Cao Jinliang Wang Yongjun Bi Jingquan Zhong Xiangbin Meng Wenyu Sun Ruixue Yang Luping Gan Xuping Wang Hongshi Li Rong Wang
author_sort	Shengya Tian
title	The miR-378c-Samd1 circuit promotes phenotypic modulation of vascular smooth muscle cells and foam cells formation in atherosclerosis lesions
title_short	The miR-378c-Samd1 circuit promotes phenotypic modulation of vascular smooth muscle cells and foam cells formation in atherosclerosis lesions
title_full	The miR-378c-Samd1 circuit promotes phenotypic modulation of vascular smooth muscle cells and foam cells formation in atherosclerosis lesions
title_fullStr	The miR-378c-Samd1 circuit promotes phenotypic modulation of vascular smooth muscle cells and foam cells formation in atherosclerosis lesions
title_full_unstemmed	The miR-378c-Samd1 circuit promotes phenotypic modulation of vascular smooth muscle cells and foam cells formation in atherosclerosis lesions
title_sort	mir-378c-samd1 circuit promotes phenotypic modulation of vascular smooth muscle cells and foam cells formation in atherosclerosis lesions
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/71186c3423784ba784512adbea8a5402
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The miR-378c-Samd1 circuit promotes phenotypic modulation of vascular smooth muscle cells and foam cells formation in atherosclerosis lesions

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