The miR-378c-Samd1 circuit promotes phenotypic modulation of vascular smooth muscle cells and foam cells formation in atherosclerosis lesions
العنوان: | The miR-378c-Samd1 circuit promotes phenotypic modulation of vascular smooth muscle cells and foam cells formation in atherosclerosis lesions |
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المؤلفون: | Wenyu Sun, Yang Cao, Xu-ping Wang, Jinliang Wang, Yongjun Bi, Ruixue Yang, Hongshi Li, Shengya Tian, Jingquan Zhong, Rong Wang, Luping Gan, Xiang-Bin Meng |
المصدر: | Scientific Reports, Vol 11, Iss 1, Pp 1-15 (2021) Scientific Reports |
بيانات النشر: | Nature Portfolio, 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | 0301 basic medicine, Vascular smooth muscle, Science, Cardiology, Down-Regulation, Diseases, Muscle, Smooth, Vascular, Article, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, microRNA, Animals, Humans, Cells, Cultured, Foam cell, Multidisciplinary, Transition (genetics), DNA-binding domain, Atherosclerosis, Phenotype, Cell biology, MicroRNAs, 030104 developmental biology, Receptors, LDL, chemistry, 030220 oncology & carcinogenesis, Medicine, Oxidation-Reduction, Sterile alpha motif, Biomarkers, DNA, Foam Cells |
الوصف: | 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. |
اللغة: | English |
تدمد: | 2045-2322 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3f60296671a8057342511c00670c78bd https://doaj.org/article/71186c3423784ba784512adbea8a5402 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....3f60296671a8057342511c00670c78bd |
قاعدة البيانات: | OpenAIRE |
تدمد: | 20452322 |
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