Faculty of Sports and Health Science, Fukuoka University.
J Atheroscler Thromb. 2016;23(4):385-94. doi: 10.5551/jat.33720. Epub 2016 Feb 1.
Clinical trials and epidemiological studies have revealed a negative correlation between serum high-density lipoprotein (HDL) cholesterol levels and the risk of cardiovascular events. Currently, statin treatment is the standard therapy for cardiovascular diseases, reducing plasma low-density lipoprotein (LDL) cholesterol levels. However, more than half of the patients have not been able to receive the beneficial effects of this treatment.The reverse cholesterol transport pathway has several potential anti-atherogenic properties. An important approach to HDL-targeted therapy is the optimization of HDL cholesterol levels and function in the blood to enhance the removal of circulating cholesterol and to prevent or mitigate inflammation that causes atherosclerosis. Cholesteryl ester transfer protein inhibitors increase HDL cholesterol levels in humans, but whether they reduce the risk of atherosclerotic diseases is unknown. HDL therapies using HDL mimetics, including reconstituted HDL, apolipoprotein (Apo) A-IMilano, ApoA-I mimetic peptides, or full-length ApoA-I, are highly effective in animal models. In particular, the Fukuoka University ApoA-I-mimetic peptide (FAMP) effectively removes cholesterol via the ABCA1 transporter and acts as an anti-atherosclerotic agent by enhancing the biological functions of HDL without elevating HDL cholesterol levels.Our literature review suggests that HDL mimetics have significant atheroprotective potential and are a therapeutic tool for atherosclerotic diseases.
临床试验和流行病学研究表明，血清高密度脂蛋白（HDL）胆固醇水平与心血管事件的风险呈负相关。目前，他汀类药物治疗是心血管疾病的标准治疗方法，可降低血浆中低密度脂蛋白（LDL）胆固醇水平。然而，超过一半的患者未能从中受益。胆固醇逆向转运途径具有多种潜在的抗动脉粥样硬化特性。HDL 靶向治疗的一个重要方法是优化血液中 HDL 胆固醇水平和功能，以增强循环胆固醇的清除，并预防或减轻导致动脉粥样硬化的炎症。胆固醇酯转移蛋白抑制剂可增加人类的 HDL 胆固醇水平，但它们是否能降低动脉粥样硬化疾病的风险尚不清楚。使用 HDL 模拟物的 HDL 治疗，包括再生性 HDL、载脂蛋白（Apo）A-IMilano、ApoA-I 模拟肽或全长 ApoA-I，在动物模型中非常有效。特别是，福冈大学的 ApoA-I 模拟肽（FAMP）通过 ABCA1 转运蛋白有效去除胆固醇，并通过增强 HDL 的生物学功能而发挥抗动脉粥样硬化作用，而不会升高 HDL 胆固醇水平。我们的文献综述表明，HDL 模拟物具有显著的动脉保护潜力，是治疗动脉粥样硬化疾病的一种治疗工具。
