Dissecting the Impact of Vascular Smooth Muscle Cell ABCA1 versus ABCG1 Expression on Cholesterol Efflux and Macrophage-like Cell Transdifferentiation: The Role of SR-BI.
Dissecting the Impact of Vascular Smooth Muscle Cell ABCA1 versus ABCG1 Expression on Cholesterol Efflux and Macrophage-like Cell Transdifferentiation: The Role of SR-BI.
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DOI：
10.3390/jcdd10100416
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发表时间：
2023-10-02
影响因子：
2.4
通讯作者：
Stamatikos A
中科院分区：
文献类型：
--
作者：
Oladosu O;Esobi IC;Powell RR;Bruce T;Stamatikos A
高胆固醇的巨噬细胞被认为是动脉粥样硬化的主要贡献者。然而，最近的证据表明，积聚胆固醇并转分化为巨噬细胞样细胞(MLC)的血管平滑肌细胞(VSMC)也在动脉粥样硬化中发挥作用。因此，从MLC中去除胆固醇可能是一种潜在的动脉粥样硬化保护策略。从细胞中去除胆固醇的两个转运体是ABCA1和Abcg1，因为它们分别将胆固醇排出到载脂蛋白AI和高密度脂蛋白。本研究通过编辑VSMC永生化细胞系Movas细胞，获得ABCA1和Abcg1基因敲除(KO)的Movas细胞系。我们负载胆固醇的ABCA1-KO Movas细胞、Abcg1-KO Movas细胞和野生型Movas细胞将细胞转化为MLC表型。当我们测量这些细胞的载脂蛋白AI和高密度脂蛋白介导的胆固醇外流时，我们观察到ABCA1-KO Movas MLC中载脂蛋白AI介导的胆固醇外流急剧减少，而高密度脂蛋白介导的胆固醇外流仅在Abcg1-KO Movas细胞中部分减少。由于SR-BI也参与了高密度脂蛋白介导的胆固醇外流，我们检测了SR-BI在Abcg1-KO Movas MLC中的表达，并观察到SR-BI的上调，这为为什么高密度脂蛋白介导的胆固醇外流在Abcg1-KO Movas MLC中保持不变提供了可能的机制。当我们在Abcg1-KO Movas MLC中使用慢病毒shRNA介导的SR-BI敲除时，与未经操纵的SR-BI表达的Abcg1-KO Movas MLC相比，这减少了高密度脂蛋白介导的胆固醇外流。综上所述，这些主要发现表明，当Abcg1表达受损时，VSMC起源的MLC中SR-BI的表达在高密度脂蛋白介导的胆固醇流出中起到补偿作用，并为SR-BI在VSMC/MLC中显示抗动脉粥样硬化特性提供了洞察。
Cholesterol-laden macrophages are recognized as a major contributor to atherosclerosis. However, recent evidence indicates that vascular smooth muscle cells (VSMC) that accumulate cholesterol and transdifferentiate into a macrophage-like cell (MLC) phenotype also play a role in atherosclerosis. Therefore, removing cholesterol from MLC may be a potential atheroprotective strategy. The two transporters which remove cholesterol from cells are ABCA1 and ABCG1, as they efflux cholesterol to apoAI and HDL, respectively. In this study, the well-characterized immortalized VSMC line MOVAS cells were edited to generate ABCA1- and ABCG1-knockout (KO) MOVAS cell lines. We cholesterol-loaded ABCA1-KO MOVAS cells, ABCG1-KO MOVAS cells, and wild-type MOVAS cells to convert cells into a MLC phenotype. When we measured apoAI- and HDL-mediated cholesterol efflux in these cells, we observed a drastic decrease in apoAI-mediated cholesterol efflux within ABCA1-KO MOVAS MLC, but HDL-mediated cholesterol efflux was only partially reduced in ABCG1-KO MOVAS cells. Since SR-BI also participates in HDL-mediated cholesterol efflux, we assessed SR-BI protein expression in ABCG1-KO MOVAS MLC and observed SR-BI upregulation, which offered a possible mechanism explaining why HDL-mediated cholesterol efflux remains maintained in ABCG1-KO MOVAS MLC. When we used lentivirus for shRNA-mediated knockdown of SR-BI in ABCG1-KO MOVAS MLC, this decreased HDL-mediated cholesterol efflux when compared to ABCG1-KO MOVAS MLC with unmanipulated SR-BI expression. Taken together, these major findings suggest that SR-BI expression in MLC of a VSMC origin plays a compensatory role in HDL-mediated cholesterol efflux when ABCG1 expression becomes impaired and provides insight on SR-BI demonstrating anti-atherogenic properties within VSMC/MLC.
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影响因子：
5.3
作者：
Esobi, Ikechukwu C.;Oladosu, Olanrewaju;Echesabal-Chen, Jing;Powell, Rhonda R.;Bruce, Terri;Stamatikos, Alexis
通讯作者：
Stamatikos, Alexis
影响因子：
64.5
作者：
Moore KJ;Tabas I
通讯作者：
Tabas I
影响因子：
3.4
作者：
Ghosh R;Gilda JE;Gomes AV
通讯作者：
Gomes AV
影响因子：
5.5
作者：
通讯作者：
--
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