Section of Cardiology, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Room 525D, Houston, TX 77030, USA.
Curr Atheroscler Rep. 2010 Sep;12(5):343-8. doi: 10.1007/s11883-010-0091-x.
High-density lipoprotein (HDL) is well established as a negative risk factor for the development of atherosclerosis. Epidemiologic, pathologic, and experimental studies have demonstrated a role for HDL in protection from coronary artery disease. HDL has been demonstrated to reduce the risk from atherosclerosis by multiple pathophysiologic mechanisms. Low-density lipoprotein is a metabolic end product that can be recognized and cleared by specific hepatic receptors with excretion into the bile. However, low-density lipoprotein may also be scavenged in the periphery by the monocyte-macrophage system, with subsequent generation of lipid-laden foam cells. HDL may reduce the atherosclerotic burden by multiple potential mechanisms. HDL can interact with the foam cell to remove cholesterol via receptor-mediated binding, passive diffusion, and alteration of intracellular cholesterol trafficking by ATP binding cassettes. The process of reverse cholesterol transport is a major mechanism by which HDL can remove cholesterol from the periphery, allowing it to be cleared by the liver and then excreted into the bile. However, HDL exhibits multiple additional potential beneficial physiologic effects. Endothelial function and repair is potentiated by HDL. Normal HDL has significant anti-inflammatory and antioxidant activity. Prostacyclin production and improvement in fibrinolytic balance is also attributed to normally functioning HDL. HDL is also intimately related to the metabolism of other circulating lipoproteins. However, multiple clinical studies have identified individuals with a significant atherosclerotic burden despite normal or elevated levels of HDL cholesterol. Clinical conditions associated with inflammation and oxidative stress have adversely altered the normal functions of HDL. Clinical assays have been developed to assess the functionality of HDL. Dysfunctional HDL may be returned to normal by diet, exercise, degree of fat intake, and pharmacologic approaches. Orally active mimetic proteins are in development and have shown clinical promise.
高密度脂蛋白（HDL）是公认的动脉粥样硬化发展的负风险因素。流行病学、病理学和实验研究表明，HDL 在预防冠状动脉疾病方面发挥作用。HDL 通过多种病理生理机制被证明可以降低动脉粥样硬化的风险。低密度脂蛋白是一种代谢终产物，可以被特定的肝脏受体识别和清除，并排入胆汁。然而，低密度脂蛋白也可能被单核细胞-巨噬细胞系统在周围组织中吞噬，随后产生富含脂质的泡沫细胞。HDL 可以通过多种潜在机制减少动脉粥样硬化负担。HDL 可以通过受体介导的结合、被动扩散和改变细胞内胆固醇转运来与泡沫细胞相互作用，从而去除胆固醇。胆固醇逆转运过程是 HDL 从周围组织中去除胆固醇的主要机制，使胆固醇可以被肝脏清除，然后排入胆汁。然而，HDL 还具有多种其他潜在的有益生理作用。HDL 增强内皮功能和修复。正常的 HDL 具有显著的抗炎和抗氧化活性。前列环素的产生和纤维蛋白溶解平衡的改善也归因于正常功能的 HDL。HDL 还与其他循环脂蛋白的代谢密切相关。然而，多项临床研究表明，尽管 HDL 胆固醇水平正常或升高，但仍有大量个体存在明显的动脉粥样硬化负担。与炎症和氧化应激相关的临床情况会对 HDL 的正常功能产生不利影响。已经开发出临床检测来评估 HDL 的功能。通过饮食、运动、脂肪摄入量和药物治疗等方法可以使功能失调的 HDL 恢复正常。具有口服活性的模拟蛋白正在开发中，并显示出临床前景。
