Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland.
Trends Pharmacol Sci. 2018 Aug;39(8):733-747. doi: 10.1016/j.tips.2018.06.001. Epub 2018 Jun 30.
Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in developed nations. Therapeutic modulation of dyslipidemia by inhibiting 3'-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is standard practice throughout the world. However, based on findings from Mendelian studies and genetic sequencing in prospective longitudinal cohorts from around the world, novel therapeutic targets regulating lipid and lipoprotein metabolism, such as apoprotein C3, angiopoietin-like proteins 3 and 4, and lipoprotein(a), have been identified. These targets may provide additional avenues to prevent and treat atherosclerotic disease. We therefore review these novel molecular targets by addressing available Mendelian and observational data, therapeutic agents in development, and early outcomes results.
动脉粥样硬化性心血管疾病（ASCVD）仍然是发达国家发病率和死亡率的主要原因。通过抑制 3'-羟基-3-甲基戊二酰基辅酶 A（HMG-CoA）还原酶来调节血脂异常是全世界的标准治疗方法。然而，基于孟德尔研究和世界各地前瞻性纵向队列的遗传测序结果，已经确定了调节脂质和脂蛋白代谢的新型治疗靶点，如载脂蛋白 C3、血管生成素样蛋白 3 和 4 以及脂蛋白（a）。这些靶点可能为预防和治疗动脉粥样硬化疾病提供额外的途径。因此，我们通过讨论现有的孟德尔和观察性数据、正在开发的治疗药物以及早期结果来回顾这些新的分子靶点。
