Background The proprotein convertase subtilisin/kexin type 9 (PCSK9) has been confirmed

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) impartial effects. 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?Rabbit polyclonal to ADCK1. and HNF1α suggesting that the role of PCSK9 in myocardial injury may be needed further study. and knockdown of gene caused not only a low plasma level of PCSK9 but also a significant decreased level of LDL-C accompanied by decreased cardiovascular risk [5 6 Recent studies have elucidated that PCSK9 is mainly synthesized by the liver and has been shown to bind to the LY450139 low-density lipoprotein receptor (LDLR) subsequently promoting its degradation [7]. This process reduces the availability of LDLR the major receptor mediating the clearance of low-density lipoprotein (LDL) particle and results in increased plasma LDL-C levels. Since elevated LDL-C has long been established as a predominant risk factor for coronary artery disease (CAD) manipulating PCSK9 level would be a promising new treatment strategy [8]. The pathogenesis of acute myocardial infarction (AMI) is usually multifactorial however several studies have indicated that hyperlipidemia is usually a major risk factor accountable for 54% of LY450139 population-attributable risk for AMI [9]. In addition previous studies have reported that during the acute stage of AMI serum lipids metabolism was severely affected [10]. 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 contamination [15] systemic inflammation [16] severe trauma injury [17] and the severity LY450139 of coronary atherosclerosis [18]. However it remains unknown whether the PCSK9 expression is usually influenced by the impact of AMI. Therefore the aim of present study was to investigate the changes of both plasma and liver PCSK9 level using the AMI rat model. Methods Animal model Adult male Sprague-Dawley rats (n?=?6-8 at each time point) weighing 260-280?g were acclimatized with a 12?hour (h) light/dark cycle at a controlled room heat of 22-24°C and rats were allowed free access to the regular and normal diet (fat content 4.62%) and clean drinking water for seven days before use. Myocardial infarction models were induced by ligation of the left anterior descending coronary artery (LAD) under ether anesthesia as previously described [19]. Electrocardiography was used to demonstrate ST elevation and thereby confirm the success of surgery. Sham operated animals (n?=?6) underwent the same procedure except that no ligation was carried out. The experimental procedures were approved by the Institutional Animal Care and Use Committee of the FuWai Hospital and conformed to Guide for the Care and Use of Laboratory Animals from National Institutes of Health. Blood and tissue sampling Prior to sacrifice 2 fasting blood samples were collected from the tail vein at 1 3 6 9 12 24 48 and 96?h post infarction LY450139 and transferred to K2 EDTA tubes. The blood samples were centrifuged and the plasma was stored at -80°C until the analyses were performed. Immediately after blood sampling the animals were sacrificed by an overdose of pentobarbital sodium. Tissue fragments from liver LY450139 were collected and snap-frozen in liquid nitrogen and stored at -80°C. Blood sample measurements Concentrations of serum total cholesterol (TC) triglycerides (TG) high-density lipoprotein-cholesterol (HDL-C) LDL-C and free fatty acid (FFA) were determined on an automatic biochemistry analyzer (Hitachi 7150 Tokyo Japan). Plasma PCSK9 concentration was measured using a high-sensitivity.