Department of Medicine, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Department of Emergency and Organ Transplants, Unit of Endocrinology, University of Bari Medical School, Bari, Italy.
Ann Hepatol. 2017 Nov;16(Suppl. 1: s3-105.):s27-s42. doi: 10.5604/01.3001.0010.5495.
Atherosclerosis is characterized by lipid accumulation, inflammatory response, cell death and fibrosis in the arterial wall, and is major pathological basis for ischemic coronary heart disease (CHD), which is the leading cause of morbidity and mortality in the USA and Europe. Intervention studies with statins have shown to reduce LDL cholesterol levels and subsequently the risk of developing CHD. However, not all the aggressive statin therapy could decrease the risk of developing CHD. Many clinical and epidemiological studies have clearly demonstrated that the HDL cholesterol is inversely associated with risk of CHD and is a critical and independent component of predicting its risk. Elucidations of HDL metabolism give rise to therapeutic targets with potential to raising plasma HDL cholesterol levels, thereby reducing the risk of developing CHD. The concept of reverse cholesterol transport is based on the hypothesis that HDL displays an cardioprotective function, which is a process involved in the removal of excess cholesterol that is accumulated in the peripheral tissues (e.g., macrophages in the aortae) by HDL, transporting it to the liver for excretion into the feces via the bile. In this review, we summarize the latest advances in the role of the lymphatic route in reverse cholesterol transport, as well as the biliary and the non-biliary pathways for removal of cholesterol from the body. These studies will greatly increase the likelihood of discovering new lipid-lowering drugs, which are more effective in the prevention and therapeutic intervention of CHD that is the major cause of human death and disability worldwide.
动脉粥样硬化的特征是脂质积聚、炎症反应、细胞死亡和动脉壁纤维化，是缺血性冠心病（CHD）的主要病理基础，在美国和欧洲是发病率和死亡率的主要原因。用他汀类药物进行的干预研究表明，降低 LDL 胆固醇水平可降低 CHD 的发病风险。然而，并非所有强化他汀类药物治疗都能降低 CHD 的发病风险。许多临床和流行病学研究清楚地表明，HDL 胆固醇与 CHD 的风险呈负相关，是预测其风险的关键和独立组成部分。对 HDL 代谢的阐明产生了具有升高血浆 HDL 胆固醇水平潜力的治疗靶点，从而降低了 CHD 的发病风险。胆固醇逆向转运的概念基于这样的假设，即 HDL 具有心脏保护功能，这是一个涉及通过 HDL 从外周组织（例如主动脉中的巨噬细胞）中清除多余胆固醇的过程，将其运送到肝脏，通过胆汁排入粪便。在这篇综述中，我们总结了在胆固醇逆向转运中淋巴途径的最新进展，以及从体内去除胆固醇的胆汁和非胆汁途径。这些研究将极大地增加发现新的降脂药物的可能性，这些药物在预防和治疗 CHD 方面更有效，CHD 是全世界人类死亡和残疾的主要原因。
