Zhang Yan, Liu Jun, Li Sha, Xu Rui-Xia, Sun Jing, Tang Yue, Li Jian-Jun
Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing 100037, China.
BMC Cardiovasc Disord. 2014 Dec 17;14:192. doi: 10.1186/1471-2261-14-192.
The proprotein convertase subtilisin/kexin type 9 (PCSK9) has been confirmed as a major factor regulating cholesterol homeostasis and has low-density lipoprotein receptor (LDLR) independent effects. In addition, the pathogenesis of acute myocardial infarction (AMI) involves lipids alteration and other acute phase responses. It remains unknown whether the PCSK9 expression is influenced by the impact of AMI. The present study aimed to investigate the changes of PCSK9 concentration using AMI rat model.
AMI (n = 6-8 at each time point) or sham operated (n = 6) adult male rats model were used. Whole blood and liver tissue were collected at 1, 3, 6, 9, 12, 24, 48, and 96 hour (h) post infarction. The plasma PCSK9 concentration was measured by ELISA and lipid profiles were measured by enzymatic assay. The liver mRNA levels of PCSK9, LDLR, sterol response element binding protein-2 (SREBP-2) and hepatocyte nuclear factor 1α (HNF1α) were measured by quantitative real-time PCR.
The plasma PCSK9 concentration was increased from 12 h to 96 h (P < 0.05 vs. control). Paralleled with the enhanced plasma PCSK9 concentration, the hepatic PCSK9 mRNA expression was up-regulated by 2.2-fold at 12 h and 4.1-fold at 24 h. Hepatic mRNA levels of LDLR, SREBP-2 and HNF1α were all increased and lipid profiles underwent great changes at this acute period.
We firstly demonstrated that PCSK9 was transiently up-regulated in the acute period of AMI, which is also driven by transcriptional factors, SREBP-2 and HNF1α, suggesting that the role of PCSK9 in myocardial injury may be needed further study.
前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）已被确认为调节胆固醇稳态的主要因素，且具有低密度脂蛋白受体（LDLR）非依赖效应。此外，急性心肌梗死（AMI）的发病机制涉及脂质改变和其他急性期反应。PCSK9表达是否受AMI影响仍不清楚。本研究旨在利用AMI大鼠模型研究PCSK9浓度的变化。
采用AMI（每个时间点n = 6 - 8）或假手术（n = 6）成年雄性大鼠模型。在梗死术后1、3、6、9、12、24、48和96小时（h）采集全血和肝组织。通过酶联免疫吸附测定（ELISA）法测定血浆PCSK9浓度，通过酶法测定血脂谱。通过定量实时聚合酶链反应（PCR）法测定肝脏中PCSK9、LDLR、固醇调节元件结合蛋白2（SREBP - 2）和肝细胞核因子1α（HNF1α）的mRNA水平。
血浆PCSK9浓度从12小时至96小时升高（与对照组相比，P < 0.05）。与血浆PCSK9浓度升高相平行，肝脏PCSK9 mRNA表达在12小时上调2.2倍，在24小时上调4.1倍。在此急性期，肝脏中LDLR、SREBP - 2和HNF1α的mRNA水平均升高，血脂谱发生了很大变化。
我们首次证明，PCSK9在AMI急性期短暂上调，且由转录因子SREBP - 2和HNF1α驱动，提示PCSK9在心肌损伤中的作用可能需要进一步研究。
