Transport of LDLs into the arterial wall: impact in atherosclerosis.
Transport of LDLs into the arterial wall: impact in atherosclerosis.
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DOI：
10.1097/mol.0000000000000701
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发表时间：
2020-10
影响因子：
4.4
通讯作者：
Fernández-Hernando C
中科院分区：
文献类型：
--
作者：
Zhang X;Fernández-Hernando C
动脉粥样硬化是一种复杂的心血管疾病，其特征是脂质代谢不平衡和动脉内部发生未解决的炎症。低密度脂蛋白（LDL）穿过内皮的转胞吞作用及其在动脉壁中的积累是动脉粥样硬化的第一步。在这里，我们总结了最近对内皮 LDL 转胞吞作用的调节机制及其与动脉粥样硬化发展的相关性的理解的研究。最近的许多研究揭示了小窝、激活素样激酶 1 (ALK1) 或清道夫受体 B1 (SR-B1) 在内皮 LDL 转胞吞作用和动脉粥样硬化进展中的作用。 Caveolin-1 (Cav-1) 是小凹的主要蛋白质成分，是小凹形成以及小凹介导的 LDL 摄取和跨内皮转胞吞作用所必需的。 SR-B1和ALK1直接结合LDL并促进LDL通过内皮细胞的转运。小窝相关蛋白和 SR-B1 表达的变化调节内皮 LDL 转胞吞作用和动脉粥样硬化的发病机制。 Caveolae、ALK1 和 SR-B1 被确定为 LDL 跨内皮转胞吞作用的关键调节因子。内皮低密度脂蛋白转胞吞作用可能是限制早期动脉粥样硬化发生和治疗动脉粥样硬化性血管疾病的潜在治疗方法。
Atherosclerosis is a complicated cardiovascular disease characterized by unbalanced lipid metabolism and unresolved inflammation that occurred inside of arteries. The transcytosis of low- density lipoprotein (LDL) across the endothelium and its accumulation in the arterial wall is the initial step of atherosclerosis. Here we summarize recent research into the understanding of the regulatory mechanisms of endothelial LDL transcytosis and its relevance in the development of atherosclerosis. A number of recent studies have revealed the contribution of caveolae, activin-like kinase 1 (ALK1) or scavenger receptor B1 (SR-B1) in endothelial LDL transcytosis and the progression of atherosclerosis. Caveolin-1 (Cav-1), the major protein component in caveolae, is required for the formation of caveolae and caveolae-mediated LDL uptake and transcytosis across the endothelium. SR-B1 and ALK1 directly bind LDL and facilitate the transport of LDL through the endothelial cells. The change in expression of caveolae-associated proteins and SR-B1 regulates endothelial LDL transcytosis and the pathogenesis of atherosclerosis. Caveolae, ALK1 and SR-B1 are identified as key regulators in the LDL transcytosis across the endothelium. Endothelial LDL transcytosis might be a potential therapeutic approach to limit the initiation of early atherosclerosis and treat the atherosclerotic vascular diseases.