Proprotein convertase subtilisin/kexin type 9 expression is transiently up-regulated in the acute period of myocardial infarction in rat.

Yan Zhang,Yue Tang,Jian-Jun Li,Jun Liu,Jing Sun,Sha Li,Rui-Xia Xu

doi:10.1186/1471-2261-14-192

Abstract

BackgroundThe 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.MethodsAMI (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.ResultsThe 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.ConclusionsWe 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.

Highlights

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
PCSK9 concentration was significantly increased at 12 h (544.18 ± 262.69 ng/ml vs. 293.53 ± 119.90 ng/ml, P < 0.05 vs. control) post acute myocardial infarction (AMI), and reached a peak level of 1647.29 ± 120.47 ng/ml (P < 0.05 vs. control) at 48 h, decreased thereafter to reach a value of 467.54 ± 155.73 ng/ml (P < 0.05 vs. control) at 96 h
In a study neutrophil to lymphocyte ratio (NLR) was found to have a significant relationship with the severity of ACS assessed by SYNTAX Score and higher NLR was found in ST elevation myocardial infarction patients [29]

Summary

Introduction

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. Whereas PCSK9, an important factor regulating cholesterol homeostasis, has been reported to be associated with a variety of physiological and pathological factors dependent or independent of the LDLR, such as statins [11], fenofibrate [12], fasting [13], sex [14], periodontal infection [15], systemic inflammation [16], severe trauma injury [17] and the severity of coronary atherosclerosis [18] It remains unknown whether the PCSK9 expression is influenced by the impact of AMI. The aim of present study was to investigate the changes of both plasma and liver PCSK9 level using the AMI rat model

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Discussion

Conclusion