Objective Very early-onset coronary artery disease(CAD) is a great challenge in cardiovascular medicine throughout the world,especially regarding its early diagnosis.This study explored whether circulating micro RNAs(mi RNAs) could be used as potential biomarkers for patients with very early-onset CAD.Methods We performed an initial screening of mi RNA expression using RNA isolated from 20 patients with angiographically documented very early-onset CAD and 20 age-and sex-matched normal controls.For further confirmation,we prospectively examined the mi RNAs selected from 40 patients with very early-onset CAD and 40 angiography-normal controls.Results A total of 22 overexpressed mi RNAs and 22 underexpressed mi RNAs were detected in the initial screening.RT-q PCR analysis of the mi RNAs obtained from the initial screening revealed that four mi RNAs including mi R-196-5p,mi R-3163-3p,mi R-145-3p,and mi R-190a-5p exhibited significantly decreased expression in patients compared with that in controls(P<0.05).The areas under the receiver operating characteristic curve for these mi RNAs were 0.824(95% CI,0.731-0.917;P<0.001),0.758(95% CI,0.651-0.864;P<0.001),0.753(95% CI,0.643-0.863;P<0.001),and 0.782(95% CI,0.680-0.884;P<0.001),respectively,in the validation set.Conclusion To our knowledge,this is an advanced study to report about four serum mi RNAs(mi R-196-5p,mi R-3163-3p,mi R-145-3p,and mi R-190a-5p) that could be used as novel biomarkers for the diagnosis of very early-onset CAD.
DU YingYANG Sheng HuaLI ShaCUI Chuan JueZHANG YanZHU Cheng GangGUO Yuan LinWU Na QiongGAO YingSUN JingDONG QianLIU GengLI Jian Jun
Objective:To investigate the short- and long-term effects of Xuezhikang(血脂康,XZK),an extract of Cholestin,on proprotein convertase subtilisin/kexin type 9(PCSK9) level.Methods:Thirty rats were randomly divided into three groups and were given saline,XZK 1,200 mg/kg or lovastatin 10 mg/kg respectively by daily gavage for 3 days(n=10 for each).Sixteen patients without previous iipid-lowering drug treatment for dyslipidemia received XZK 1,200 mg daily for 8 weeks.Fasting blood samples and liver tissue were collected at day 3 for rats,while the blood samples were obtained at baseline and week 8 from patients.The serum PCSK9 and lipid profile were measured.The expression of hepatic low density lipoprotein(LDL) receptor and sterol regulatory element binding protein 2(SREBP-2) were measured by real time-PCR.Results:PCSK9 levels in rats were significantly increased in the XZK and lovastatin groups(P=0.002,P=0.003 vs.control) at day 3,while no significant differences were found in the levels of lipid parameters.PCSK9 levels in patients increased by34%(P=0.006 vs.baseline) accompanied by total cholesterol and LDL-cholesterol decreased by 22%and 28%(P=0.001,P=0.002 vs.baseline).The hepatic mRNA levels of LDL-receptor and SREBP-2 were significantly increased in the XZK and lovastatin groups.Conclusion:XZK has significant impact on PCSK9 in a short- and long-term manner in both rats and humans.Moreover,the data indicated that as lovastatin,XZK increased PCSK9 levels through SREBP-2 pathway.
动脉粥样硬化( atherosclerosis,AS)的形成过程极其复杂,其发病机制涉及炎性反应、脂质代谢失调及氧化应激等多种病理生理机制[1-3]。其中,低密度脂蛋白胆固醇(low density lipoprotein cholesterin,LDL-C)的氧化修饰被认为是AS形成的关键启动因素[4]。
