Proprotein convertase subtilisin kexin-9 level remains unchanged following glucocorticoid-induced dyslipidemia in Wistar rats

Abstract

Proprotein convertase subtilisin kexin type 9 (PCSK9) is a secreted liver enzyme that regulates low-density lipoproteins and is dysregulated in dyslipidemia of various etiology. Glucocorticoids are powerful anti-inflammatory agents that also induce dyslipidemia. The role of PCSK9 in glucocorticoid-induced dyslipidemia remains underexplored. In this study, we investigate sex-dependent changes in serum PCSK9 levels following glucocorticoid-induced dyslipidemia. Fourteen male and fourteen female Wistar rats, eight weeks old were administered normal saline or dexamethasone (dex) 2 mg/kg via the intraperitoneal route for seven consecutive days. Six hours after the last dose, cardiac blood was collected from anesthetized animals. Serum was analyzed for lipid profile, sex hormones and enzyme concentration using enzyme-linked immunosorbent assays. Data were analyzed using one-way analysis of variance followed by Sidak’s test. Significance was accepted at p ≤ 0.05. Dexamethasone administration induced significant hypercholesterolemia (94.55 ± 1.676 vs 150.6 ± 11 mg/dL; p < 0.0001) and dyslipidemia (24.13 ± 4.11 vs 72.46 ± 8.883 mg/dL; p < 0.0001) in both male and female rats. There was a trend towards increased circulating PCSK9 however increases were not statistically significant. Dexamethasone induced dyslipidemia without altering plasma concentration of PCSK9.