后他汀药物PCSK-9抑制剂研究进展.pptVIP

New words low-density lipoprotein cholesterol LDL-C 低密度脂蛋白[k?lest?r?l] Proprotein convertase subtilisin kexin type 9 PCSK9（前蛋白转化酶枯草溶菌素9/神经细胞凋亡调节转化酶-1 ）[s?btilisin]? cardiovascular CV 心血管 endosome [‘end?,s?um]?内涵体 释放与细胞内吞 Golgi 高尔基体 分泌为主要功能的细胞器 Lysosomal [‘lais?s?um?]溶酶体 消化作用 Deciliter [‘des??li:t?] 分升 Dyslipidemia [d?sl?p?‘dem??] 血脂异常 PCSK9 plasma levels were highly correlated with blood LDL-C Statin treatment and PCSK9 PhaseⅢ clinical trials 3 new drugs Thank you * * /viewarticle/836415 LDL-C and CV ?risk LDL-C＞1.3mmol/L(50mg/dL) Residual CV Risk Combination Therapy LDLR Statin PCSK-9mAb SREBP-2 PCSK-9 + + - - + Sterol Response Element Binding Protein-2 PCSK9 and LDL-R Brautbar, A. Ballantyne, C. M. Nat. Rev. Cardiol. 8, 253–265 (2011) PCSK9 inhibitor ＞LDL-C 40% statins is used widely in cardiovascular field to lower blood lipids，especially LDL-C。this slide showed approximate dose equivalency of stain LDL-C efficacy。From this picture showed that for example 40mg Rosuvastatin equal to 80mg Atorvastatin，can lower LDL-C 51%-55% LDL-c has tightly relation to CV event。If LDL-c level more than 1.3mmol per liters，whith the LDL-c decreased，the absolutely CV risk also decreased Despite the use of?high-dose statin,clinic trial showed still have residual risk In order to?control the level of LDL-c,?in addition to high?dose statin,?another method?is Combination therapy Retrospective study showed that PCSK9 plasma levels were highly correlated with blood LDL-C.the Table showed that the Spearman correlation coefficient between PCSK9 and LDL-C is 0.29 in woman，and 0.26 in man statin treatment also Bring another problem is may increase LDL-R level。From this picture we can know that statin treatment can reduce LDLR level through increased SREBP-2。But increased SREBP-2 can increase PCSK9，PCSK9 can increase LDLR。So PCSK9?inhibitors can improve?the?effect?of statins LDL-R have three?degradation pathway. firstly LDL particles?bi