MOVAS Cells: A Versatile Cell Line for Studying Vascular Smooth Muscle Cell Cholesterol Metabolism.
MOVAS Cells: A Versatile Cell Line for Studying Vascular Smooth Muscle Cell Cholesterol Metabolism.
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DOI：
10.1002/lipd.12303
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发表时间：
2021-07
期刊：
影响因子：
1.9
通讯作者：
Stamatikos A
中科院分区：
文献类型：
--
作者：
Esobi IC;Barksdale C;Heard-Tate C;Reigers Powell R;Bruce TF;Stamatikos A
胆固醇代谢对细胞至关重要。胆固醇代谢异常影响胆固醇稳态，可能影响多种疾病的风险。最近有证据表明血管平滑肌细胞（VSMC）胆固醇代谢可能在动脉粥样硬化中起作用。然而，缺乏与原发性VSMC有关的体外机制数据，直接测试VSMC胆固醇代谢如何影响动脉粥样硬化。缺乏数据的一个原因是由于基因操作研究在原代VSMC中的不可行性，因为培养的原代VSMC会衰老并迅速失去其形态。然而，没有已知的永生化VSMC系适合研究VSMC胆固醇代谢。本研究的目的是确定MOVAS细胞（一种市售的VSMC细胞系）是否适合用于研究VSMC胆固醇代谢。通过免疫印迹和免疫荧光，我们发现MOVAS细胞表达ABCA1、ABCG1和SREBP-2。我们还确定MOVAS细胞将胆固醇外排到apoAI和HDL，这表明ABCA1/ABCG1的功能。在血清饥饿的MOVAS细胞中，SREBP-2靶基因表达增加，证实了SREBP-2的功能。我们检测了miR-33a在MOVAS细胞中的表达，并通过鉴定MOVAS细胞中ABCA1/ABCG1 3 ' utr中保守的miR-33a结合位点，确定了该microRNA可以沉默ABCA1和ABCG1。我们发现装载胆固醇的MOVAS细胞导致该细胞系转分化为巨噬细胞样细胞，这也发生在VSMC积聚胆固醇时。我们对MOVAS细胞的表征充分证明了它们适合用于研究动脉粥样硬化背景下VSMC胆固醇代谢。
Cholesterol metabolism is paramount to cells. Aberrations to cholesterol metabolism affects cholesterol homeostasis, which may impact the risk of several diseases. Recent evidence has suggested that vascular smooth muscle cell (VSMC) cholesterol metabolism may play a role in atherosclerosis. However, there is scant in vitro mechanistic data involving primary VSMC that directly tests how VSMC cholesterol metabolism may impact atherosclerosis. One reason for this lack of data is due to the impracticality of gene manipulation studies in primary VSMC, as cultured primary VSMC become senescent and lose their morphology rapidly. However, there are no immortalized VSMC lines known to be suitable for studying VSMC cholesterol metabolism. The purpose of this study was to determine whether MOVAS cells, a commercially available VSMC line, are suitable to use for studying VSMC cholesterol metabolism. Using immunoblotting and immunofluorescence, we showed that MOVAS cells express ABCA1, ABCG1, and SREBP-2. We also determined that MOVAS cells efflux cholesterol to apoAI and HDL, which indicates functionality of ABCA1/ABCG1. In serum-starved MOVAS cells, SREBP-2 target gene expression was increased, confirming SREBP-2 functionality. We detected miR-33a expression in MOVAS cells and determined this microRNA can silence ABCA1 and ABCG1 via identifying conserved miR-33a binding sites within ABCA1/ABCG1 3’UTRs in MOVAS cells. We showed that cholesterol-loading MOVAS cells results in this cell line to transdifferentiate into a macrophage-like cell, which also occurs when VSMC accumulate cholesterol. Our characterization of MOVAS cells sufficiently demonstrates that they are suitable to use for studying VSMC cholesterol metabolism in the context of atherosclerosis.
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DOI：
10.1126/science.1189123
发表时间：
2010-06-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Najafi-Shoushtari SH;Kristo F;Li Y;Shioda T;Cohen DE;Gerszten RE;Näär AM
通讯作者：
Näär AM
影响因子：
--
作者：
Milioti N;Bermudez-Fajardo A;Penichet ML;Oviedo-Orta E
通讯作者：
Oviedo-Orta E
影响因子：
5.3
作者：
Goedeke, Leigh;Vales-Lara, Frances M.;Fernandez-Hernando, Carlos
通讯作者：
Fernandez-Hernando, Carlos
DOI：
10.1161/atvbaha.112.300639
发表时间：
2013-03
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Marquart TJ;Wu J;Lusis AJ;Baldán Á
通讯作者：
Baldán Á
DOI：
10.1126/science.1189862
发表时间：
2010-06-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Rayner KJ;Suárez Y;Dávalos A;Parathath S;Fitzgerald ML;Tamehiro N;Fisher EA;Moore KJ;Fernández-Hernando C
通讯作者：
Fernández-Hernando C