Rader Daniel J
Departments of Genetics and Medicine and Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell Metab. 2016 Mar 8;23(3):405-12. doi: 10.1016/j.cmet.2016.01.005. Epub 2016 Feb 4.
Dyslipidemia is a risk factor for atherosclerotic cardiovascular disease (ASCVD). Abundant data indicate that low-density lipoproteins (LDL) are causal for ASCVD; a new class of LDL-lowering medicines, the PCSK9 inhibitors, will address much unmet medical need. Human genetics suggest that triglyceride-rich lipoproteins (TRL) are pro-atherogenic and have pointed to a number of protein regulators of lipoprotein lipase activity that are candidates for therapeutic targeting. Finally, high-density lipoprotein (HDL) cholesterol does not appear to be causally associated with protection from ASCVD, reinforced by the failure of three CETP inhibitors in CV outcome trials, but HDL function remains of interest.
血脂异常是动脉粥样硬化性心血管疾病(ASCVD)的一个危险因素。大量数据表明,低密度脂蛋白(LDL)是ASCVD的病因;一类新型的降低LDL的药物,即前蛋白转化酶枯草溶菌素9(PCSK9)抑制剂,将满足许多未被满足的医疗需求。人类遗传学研究表明,富含甘油三酯的脂蛋白(TRL)具有促动脉粥样硬化作用,并指出了一些脂蛋白脂肪酶活性的蛋白质调节剂,它们是治疗靶点的候选物。最后,高密度脂蛋白(HDL)胆固醇似乎与预防ASCVD没有因果关系,三项胆固醇酯转移蛋白(CETP)抑制剂在心血管结局试验中的失败进一步证实了这一点,但HDL的功能仍然值得关注。