1] UMR INSERM-UPMC 1166 ICAN, National Institute for Health and Medical Research, Université Pierre et Marie Curie-Paris 6, AP-HP, Pitié-Salpétrière University Hospital, ICAN, Paris, France [2] Heart Institute-InCor, University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil.
UMR INSERM-UPMC 1166 ICAN, National Institute for Health and Medical Research, Université Pierre et Marie Curie-Paris 6, AP-HP, Pitié-Salpétrière University Hospital, ICAN, Paris, France.
Clin Pharmacol Ther. 2014 Jul;96(1):57-63. doi: 10.1038/clpt.2014.85. Epub 2014 Apr 11.
Cardiovascular diseases (CVDs) are the leading cause of morbidity/mortality worldwide. Dyslipidemia is a major risk factor for premature atherosclerosis and CVD. Lowering low-density-lipoprotein cholesterol (LDL-C) levels is well established as an intervention for the reduction of CVDs. Statins are the first-line drugs for treatment of dyslipidemia, but they do not address all CVD risk. Development of novel therapies is ongoing and includes the following: (i) reduction of LDL-C concentrations using antibodies to proprotein convertase subtilisin/kexin-9, antisense oligonucleotide inhibitors of apolipoprotein B production, microsomal transfer protein (MTP) inhibitors, and acyl-coenzyme A cholesterol acyl transferase inhibitors; (ii) reduction in levels of triglyceride-rich lipoproteins with ω-3 fatty acids, MTP inhibitors, and diacylglycerol acyl transferase-1 inhibitors; and (iii) increase of high-density-lipoprotein (HDL) cholesterol levels, HDL particle numbers, and/or HDL functionality using cholesteryl ester transfer protein inhibitors, HDL-derived agents, apolipoprotein AI mimetic peptides, and microRNAs. Large prospective outcome trials of several of these emerging therapies are under way, and thrilling progress in the field of lipid management is anticipated.
心血管疾病 (CVDs) 是全球发病率和死亡率的主要原因。血脂异常是动脉粥样硬化和 CVD 发生的主要危险因素。降低低密度脂蛋白胆固醇 (LDL-C) 水平已被证实是减少 CVD 的干预措施。他汀类药物是治疗血脂异常的一线药物，但它们并不能解决所有 CVD 风险。新型疗法的开发正在进行中，包括：(i) 使用针对前蛋白转化酶枯草溶菌素/激肽释放酶-9 的抗体、载脂蛋白 B 产生的反义寡核苷酸抑制剂、微粒体转移蛋白 (MTP) 抑制剂和酰基辅酶 A 胆固醇酰基转移酶抑制剂降低 LDL-C 浓度；(ii) 用 ω-3 脂肪酸、MTP 抑制剂和二酰基甘油酰基转移酶-1 抑制剂降低富含甘油三酯的脂蛋白水平；(iii) 使用胆固醇酯转移蛋白抑制剂、高密度脂蛋白 (HDL) 衍生剂、载脂蛋白 AI 模拟肽和 microRNAs 增加 HDL 胆固醇水平、HDL 颗粒数和/或 HDL 功能。这些新兴疗法的几项大型前瞻性结局试验正在进行中，预计脂质管理领域将取得激动人心的进展。
