miR-33a Expression Attenuates ABCA1-Dependent Cholesterol Efflux and Promotes Macrophage-Like Cell Transdifferentiation in Cultured Vascular Smooth Muscle Cells.
miR-33a Expression Attenuates ABCA1-Dependent Cholesterol Efflux and Promotes Macrophage-Like Cell Transdifferentiation in Cultured Vascular Smooth Muscle Cells.
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DOI：
10.1155/2023/8241899
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发表时间：
2023
影响因子：
5.3
通讯作者：
Stamatikos, Alexis
中科院分区：
文献类型：
--
作者：
Esobi, Ikechukwu C.;Oladosu, Olanrewaju;Echesabal-Chen, Jing;Powell, Rhonda R.;Bruce, Terri;Stamatikos, Alexis
最近的证据表明，动脉粥样硬化病变中发现的大多数胆固醇负载细胞是转分化为巨噬细胞样细胞（MLC）的血管平滑肌细胞（VSMC）。此外，VSMC来源的胆固醇负载MLC已证明ABCA 1依赖性胆固醇流出受损，但对其发生原因知之甚少。一种可能的机制是miR-33 a表达，这种机制至少部分归因于负载胆固醇的MLC，证明ABCA 1依赖性胆固醇流出减弱，因为这种microRNA的主要功能是沉默ABCA 1表达，但这还有待严格研究。因此，VSMC系MOVAS细胞用于产生miR-33 a敲除（KO）MOVAS细胞，并且我们使用KO和野生型（WT）MOVAS细胞来描绘miR-33 a表达在VSMC中的任何可能的促动脉粥样硬化作用。当WT和KO MOVAS细胞负载胆固醇以转化为MLC时，这导致WT MOVAS细胞表现出受损的ABCA 1依赖性胆固醇流出。在胆固醇负载的WT MOVAS MLC中，我们还观察到当这些细胞暴露于ABCA 1胆固醇受体apoAI时，VSMC表型的延迟恢复。这些结果表明，VSMC中的miR-33 a表达通过减弱ABCA 1依赖性胆固醇流出触发MLC转分化来驱动动脉粥样硬化。
Recent evidence suggests that the majority of cholesterol-laden cells found in atherosclerotic lesions are vascular smooth muscle cells (VSMC) that have transdifferentiated into macrophage-like cells (MLC). Furthermore, cholesterol-laden MLC of VSMC origin have demonstrated impaired ABCA1-dependent cholesterol efflux, but it is poorly understood why this occurs. A possible mechanism which may at least partially be attributed to cholesterol-laden MLC demonstrating attenuated ABCA1-dependent cholesterol efflux is a miR-33a expression, as a primary function of this microRNA is to silence ABCA1 expression, but this has yet to be rigorously investigated. Therefore, the VSMC line MOVAS cells were used to generate miR-33a knockout (KO) MOVAS cells, and we used KO and wild-type (WT) MOVAS cells to delineate any possible proatherogenic role of miR-33a expression in VSMC. When WT and KO MOVAS cells were cholesterol-loaded to convert into MLC, this resulted in the WT MOVAS cells to exhibit impaired ABCA1-dependent cholesterol efflux. In the cholesterol-loaded WT MOVAS MLC, we also observed a delayed restoration of the VSMC phenotype when these cells were exposed to the ABCA1 cholesterol acceptor, apoAI. These results imply that miR-33a expression in VSMC drives atherosclerosis by triggering MLC transdifferentiation via attenuated ABCA1-dependent cholesterol efflux.
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影响因子：
5.5
作者：
通讯作者：
--
影响因子：
5.3
作者：
Fitzgerald ML;Mujawar Z;Tamehiro N
通讯作者：
Tamehiro N
影响因子：
1.9
作者：
Esobi IC;Barksdale C;Heard-Tate C;Reigers Powell R;Bruce TF;Stamatikos A
通讯作者：
Stamatikos A
影响因子：
5.3
作者：
Andreeva, ER;Pugach, IM;Orekhov, AN
通讯作者：
Orekhov, AN
影响因子：
5.3
作者：
Goedeke, Leigh;Vales-Lara, Frances M.;Fernandez-Hernando, Carlos
通讯作者：
Fernandez-Hernando, Carlos