title: Proprotein convertase subtilisin/kexin type 9 expression is transiently up-regulated in the acute period of myocardial infarction in rat.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.forename: Rui-Xia
authors.initials: RX
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: 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. tangyue1226@vip.sina.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Tang
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Li
mesh_terms: D000818:Animals; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D007958:Leukocyte Count; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism*; D000071449:Proprotein Convertase 9; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000378:metabolism; D012697:Serine Endopeptidases / Q000097:blood / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D051538:Hepatocyte Nuclear Factor 1-alpha; D008055:Lipids; D012333:RNA, Messenger; D011973:Receptors, LDL; C510804:PCSK9 protein, rat; D000071449:Proprotein Convertase 9; D012697:Serine Endopeptidases