Myocardin suppression increases lipid retention and atherosclerosis via downregulation of ABCA1 in vascular smooth muscle cells
| Autor: | Ling-Yan Chen, Rui-Zhe Yang, Yao-Guang Feng, Heng Li, Xiao-Hua Yu, Song-lin Xie, Gang Wang, Chao-Ke Tang, Zhen-Wang Zhao, Xiao-Dan Xia |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Vascular smooth muscle Apolipoprotein B Mice Knockout ApoE Down-Regulation 030204 cardiovascular system & hematology Muscle Smooth Vascular 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Internal medicine medicine Animals Humans Molecular Biology Aorta Cells Cultured Aged Aged 80 and over Gene knockdown biology Cholesterol Nuclear Proteins Cell Biology Middle Aged Atherosclerosis Lipid Metabolism 030104 developmental biology Endocrinology chemistry Myocardin ABCA1 cardiovascular system biology.protein Trans-Activators lipids (amino acids peptides and proteins) Female Intracellular ATP Binding Cassette Transporter 1 |
| Zdroj: | Biochimica et biophysica acta. Molecular and cell biology of lipids. 1866(4) |
| ISSN: | 1879-2618 |
| Popis: | Myocardin (MYOCD) plays an important role in cardiovascular disease. However, its underlying impact on atherosclerosis remains to be elucidated. ATP binding cassette transporter A1 (ABCA1), a key membrane-associated lipid transporter which maintains intracellular lipid homeostasis, has a protective function in atherosclerosis progress. The purpose of this study was to investigate whether and how the effect of MYOCD on atherosclerosis is associated with ABCA1 in vascular smooth muscle cells (VSMCs). We found both MYOCD and ABCA1 expression were dramatically decreased in atherosclerotic patient aortas compared to control. MYOCD knockdown inhibited ABCA1 expression in human aortic vascular smooth muscle cells (HAVSMCs), leading to reduced cholesterol efflux and increased intracellular cholesterol contents. MYOCD overexpression exerted the opposite effect. Mechanistically, MYOCD regulates ABCA1 expression in an SRF-dependent manner. Consistently, apolipoprotein E-deficient mice treated with MYOCD shRNA developed more plaques in the aortic sinus, which is associated with reduced ABCA1 expression, increased cholesterol retention in the aorta, and decreased high-density lipoprotein cholesterol levels in the plasma. Our data suggest that MYOCD deficiency exacerbates atherosclerosis by downregulating ABCA1 dependent cholesterol efflux from VSMCs, thereby providing a novel strategy for the therapeutic treatment of atherosclerotic cardiovascular disease. |
| Databáze: | OpenAIRE |
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