Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors.
Cholesteryl ester transfer protein: at the heart of the action of lipid-modulating therapy with statins, fibrates, niacin, and cholesteryl ester transfer protein inhibitors.
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DOI：
10.1093/eurheartj/ehp399
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发表时间：
2010-01
影响因子：
39.3
通讯作者：
Kontush A
中科院分区：
文献类型：
--
作者：
Chapman MJ;Le Goff W;Guerin M;Kontush A
低于正常的高密度脂蛋白胆固醇（HDL-C）血浆水平构成了主要的心血管风险因素;因此，升高低HDL-C水平可能会降低尽管接受他汀类药物治疗但血脂异常受试者中经常出现的残余心血管风险。胆固醇酯转运蛋白（CETP）不仅是HDL和载脂蛋白（apo）A-I血管内代谢的关键调节剂，也是富含甘油三酯（TG）颗粒和低密度脂蛋白（LDL）血管内代谢的关键调节剂，它介导胆固醇酯从HDL向促动脉粥样硬化的apoB-脂蛋白的转运，其中TG主要从极低密度脂蛋白向HDL的异源转运。胆固醇酯转运蛋白活性在涉及胰岛素抵抗和中度至显著高脂血症的代谢性疾病的血脂异常中升高，并且与过早动脉粥样硬化和高心血管风险密切相关。因此，胆固醇酯转移蛋白抑制剂是升高HDL-C和减少动脉粥样硬化的首选靶点。本文综述了CETP在目前具有HDL升高潜力的调脂药物（即他汀类药物、贝特类药物和烟酸）的作用中的核心作用，并将其作用机制与正在开发的直接抑制CETP的药物进行了比较。新的CETP抑制剂，如达塞曲匹和安塞曲匹，靶向使HDL/apoA-I水平和HDL颗粒的抗动脉粥样硬化活性正常化。对这些CETP抑制剂的进一步研究，特别是在长期、大规模的结局试验中，将提供有关其在降低心血管残余风险方面的安全性和有效性的重要信息。
Subnormal plasma levels of high-density lipoprotein cholesterol (HDL-C) constitute a major cardiovascular risk factor; raising low HDL-C levels may therefore reduce the residual cardiovascular risk that frequently presents in dyslipidaemic subjects despite statin therapy. Cholesteryl ester transfer protein (CETP), a key modulator not only of the intravascular metabolism of HDL and apolipoprotein (apo) A-I but also of triglyceride (TG)-rich particles and low-density lipoprotein (LDL), mediates the transfer of cholesteryl esters from HDL to pro-atherogenic apoB-lipoproteins, with heterotransfer of TG mainly from very low-density lipoprotein to HDL. Cholesteryl ester transfer protein activity is elevated in the dyslipidaemias of metabolic disease involving insulin resistance and moderate to marked hypertriglyceridaemia, and is intimately associated with premature atherosclerosis and high cardiovascular risk. Cholesteryl ester transfer protein inhibition therefore presents a preferential target for elevation of HDL-C and reduction in atherosclerosis. This review appraises recent evidence for a central role of CETP in the action of current lipid-modulating agents with HDL-raising potential, i.e. statins, fibrates, and niacin, and compares their mechanisms of action with those of pharmacological agents under development which directly inhibit CETP. New CETP inhibitors, such as dalcetrapib and anacetrapib, are targeted to normalize HDL/apoA-I levels and anti-atherogenic activities of HDL particles. Further studies of these CETP inhibitors, in particular in long-term, large-scale outcome trials, will provide essential information on their safety and efficacy in reducing residual cardiovascular risk.
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影响因子：
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作者：
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通讯作者：
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发表时间：
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