Role of ABCA1 in Cardiovascular Disease
Role of ABCA1 in Cardiovascular Disease
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DOI：
10.3390/jpm12061010
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发表时间：
2022-06-20
影响因子：
--
通讯作者：
Ding, Hu
中科院分区：
文献类型：
--
作者：
Wang, Jing;Xiao, Qianqian;Wang, Luyun;Wang, Yan;Wang, Daowen;Ding, Hu
关键词：
胆固醇稳态在心血管疾病中起着重要作用。研究表明，ATP结合盒转运蛋白A1（ABCA 1）是维持胆固醇稳态的重要蛋白质之一。ABCA 1介导新生高密度脂蛋白生物合成。在与载脂蛋白A-I结合后，ABCA 1促进过量细胞内胆固醇和磷脂的流出，并控制胆固醇逆向转运的限速步骤。此外，ABCA 1与载脂蛋白受体相互作用，并通过一系列信号通路抑制炎症。因此，ABCA 1可以通过抑制炎症和维持脂质稳态来预防心血管疾病。许多研究表明，转录后修饰在ABCA 1的转运和质膜定位的调控中起着关键作用，从而影响其生物学功能。同时，ABCA 1基因功能缺失的携带者往往伴随着ABCA 1表达的降低和心血管疾病风险的增加。本文综述了ABCA 1的转录调控机制、突变、翻译后修饰及其在血脂异常、动脉粥样硬化、缺血/再灌注、心肌梗死和冠心病发生发展中的作用。
Cholesterol homeostasis plays a significant role in cardiovascular disease. Previous studies have indicated that ATP-binding cassette transporter A1 (ABCA1) is one of the most important proteins that maintains cholesterol homeostasis. ABCA1 mediates nascent high-density lipoprotein biogenesis. Upon binding with apolipoprotein A-I, ABCA1 facilitates the efflux of excess intracellular cholesterol and phospholipids and controls the rate-limiting step of reverse cholesterol transport. In addition, ABCA1 interacts with the apolipoprotein receptor and suppresses inflammation through a series of signaling pathways. Thus, ABCA1 may prevent cardiovascular disease by inhibiting inflammation and maintaining lipid homeostasis. Several studies have indicated that post-transcriptional modifications play a critical role in the regulation of ABCA1 transportation and plasma membrane localization, which affects its biological function. Meanwhile, carriers of the loss-of-function ABCA1 gene are often accompanied by decreased expression of ABCA1 and an increased risk of cardiovascular diseases. We summarized the ABCA1 transcription regulation mechanism, mutations, post-translational modifications, and their roles in the development of dyslipidemia, atherosclerosis, ischemia/reperfusion, myocardial infarction, and coronary heart disease.
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6.6
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