提示: 手机请竖屏浏览!

通过抑制PCSK9减少心血管事件
PCSK9 Inhibition to Reduce Cardiovascular Events


Robin P.F. Dullaart ... 心脑血管疾病 • 2017.05.04
相关阅读
• LDL究竟应降到多低 • bococizumab降脂效果的变异性和抗药抗体的产生 • 高危患者使用bococizumab的心血管疗效和安全性 • 抗药抗体生成是否为PCSK9治疗中面临的问题

2003年人们发现编码前蛋白转化酶枯草溶菌素9(PCSK9)的基因发生的功能获得性突变可引起常染色体显性遗传性高胆固醇血症,紧接着在2005年发现PCSK9发生的功能丧失性突变可引起低密度脂蛋白(LDL)胆固醇水平降低。从此,人们对于PCSK9通路的兴趣开始爆发。PCSK9是一种分泌型丝氨酸蛋白酶,它与LDL受体的细胞外结构域结合,靶向LDL受体至溶酶体腔室,使LDL受体降解1。因此,PCSK9可以阻止LDL受体向细胞表面再循环,进而减少LDL清除。PCSK9存在于人血浆中,在一定程度上与脂蛋白颗粒相关2。载脂蛋白B是LDL的主要蛋白组分,循环PCSK9水平较高预示着载脂蛋白B分解代谢较低3。这表明血浆PCSK9浓度的个体间差异有重要的病理生理学意义。





作者信息

Robin P.F. Dullaart, M.D., Ph.D.
From the Department of Endocrinology, University of Groningen, University Medical Center, Groningen, the Netherlands.

 

参考文献

1. Marais DA, Blom DJ, Petrides F, Gouëffic Y, Lambert G. Proprotein convertase subtilisin/kexin type 9 inhibition. Curr Opin Lipidol 2012;23:511-517

2. Kwakernaak AJ, Lambert G, Dullaart RP. Plasma proprotein convertase subtilisin-kexin type 9 is predominantly related to intermediate density lipoproteins. Clin Biochem 2014;47:679-682

3. Chan DC, Lambert G, Barrett PH, Rye KA, Ooi EM, Watts GF. Plasma proprotein convertase subtilisin/kexin type 9: a marker of LDL apolipoprotein B-100 catabolism? Clin Chem 2009;55:2049-2052

4. Watts GF, Chan DC, Dent R, et al. Factorial effects of evolocumab and atorvastatin on lipoprotein metabolism. Circulation 2017;135:338-351

5. Sabatine MS, Giugliano RP, Wiviott SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 2015;372:1500-1509

6. Desai NR, Giugliano RP, Wasserman SM, et al. Association between circulating baseline proprotein convertase subtilisin kexin type 9 levels and efficacy of evolocumab. JAMA Cardiol 2017 January 25 (Epub ahead of print)

7. Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015;372:1489-1499

8. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017;376:1713-1722

9. Colhoun HM, Ginsberg HN, Robinson JG, et al. No effect of PCSK9 inhibitor alirocumab on the incidence of diabetes in a pooled analysis from 10 ODYSSEY Phase 3 studies. Eur Heart J 2016;37:2981-2989

10. Landmesser U, John Chapman M, Farnier M, et al. European Society of Cardiology/European Atherosclerosis Society Task Force consensus statement on proprotein convertase subtilisin/kexin type 9 inhibitors: practical guidance for use in patients at very high cardiovascular risk. Eur Heart J 2016 October 27 (Epub ahead of print)

服务条款 | 隐私政策 | 联系我们