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 microRNAs （miRNAs） could be used as potential biomarkers for patients with very early-onset CAD. Methods We performed an initial screening of miRNA 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 miRNAs selected from 40 patients with very early-onset CAD and 40 angiography-normal controls. Results A total of 22 overexpressed miRNAs and 22 underexpressed miRNAs were detected in the initial screening. RT-qPCR analysis of the miRNAs obtained from the initial screening revealed that four miRNAs including miR-196-5p, miR-3163-3p, miR-145-3p, and miR-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 miRNAs 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 miRNAs （miR-196-5p, miR-3163-3p, miR-145-3p, and miR-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.
