The effect of statins on PCSK9 and LDLR gene expression in experimentally dyslipidemic rats

N. N. Alhafidh; M. M. Khalaf; N. G. Muustafa

doi:10.15421/0226001

N. N. Alhafidh College of Pharmacy
M. M. Khalaf College of Pharmacy
N. G. Muustafa College of Veterinary Medicine University of Mosul

Keywords: Dyslipidemia, LDLR, PCSK9, rats, statins.

Abstract

Dyslipidemia, is a well-established major risk factor for atherosclerotic cardiovascular disease (ASCVD). Low- density lipoprotein ch olesterol (LDL-C) serves as the primary transporter of cholesterol within the bloodstream. The LDLR is influenced by multiple factors, including statins and the proprotein convertase subtilisin/kexin type 9 (PCSK9). Therefore, this study aims to evaluate the effect of 2 types of statins on PCSK9 and LDLR gene expression in dyslipidemic rats. The objective of this work was to induce dyslipidemia in adult male rats by the administration of a high-fat diet. The 36 adult rats used were categorized into: t he control group (C) , which was administered a standard diet for 8 weeks, while dyslipidemia was induced in the rest of the animal groups (A, D) by a high-fat diet for 8 weeks (dy s lipidemia groups). The dyslipidemic groups were treated with two types of statins ( p itavastatin and a torvastatin) for a duration of 4 weeks. The gene expression of PCSK9 and LDLR was subsequently evaluated. Pitavastatin led to an approximately 15-fold increase, while atorvastatin result ed in approximately an 18-fold increase in PCSK9 gene expre s sion relative to pretreatment values. Regarding LDLR, pitavastatin result ed in approximately a 7-fold increase, while atorvastatin result ed in approximately a 2-fold increase in LDLR gene expression in comparison to pretreatment values. It can be concluded that treatment with both statins over 4 weeks caused an increase in the expression of LDLR and PCSK9 genes, where atorvastatin wa s slightly more effective in increasing PCSK9 gene expression and pitavastatin wa s more effective in increasing LDLR gene expression.

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