Increased expression and catalytic activity of prostacyclin synthase after simvastatin application to human umbilical vein endothelial cells

• Main Authors: Cho Sun-Ah, Lee Su-Jun
• Format: Article
• Language: English
• Published: University of Belgrade, University of Novi Sad 2020-01-01
• Series: Archives of Biological Sciences
• Subjects: prostacyclin; prostacyclin synthase; cyp8a1; simvastatin; car; cardiovascular disease
• Online Access: http://www.doiserbia.nb.rs/img/doi/0354-4664/2020/0354-46642000050C.pdf

In addition to lowering blood cholesterol levels, statins are known to exert antiplatelet effects. One of the key factors contributing to the antiplatelet effects of statins includes the upregulation of prostacyclin (PGI2) level. The present study was undertaken to determine the effects of statins on prostacyclin synthase (PGIS, CYP8A1) and PGI2 synthesis at the molecular level. Human umbilical vein endothelial cells (HUVEC) were exposed to five structurally different statins (atorvastatin, simvastatin, pravastatin, lovastatin, and rosuvastatin) and changes in CYP8A1 expression levels and the metabolic activities of CYP8A1 were investigated. Among the tested statins, simvastatin induced significant PGIS expression at both transcriptional (2.9-fold, P<0.05) and translational (1.8-fold, P<0.05) levels. Treatment with a constitutive androstane receptor (CAR) agonist, phenobarbital, significantly increased CYP8A1 mRNA expression (3-fold, P<0.01). A metabolite of prostacyclin, 6-keto prostaglandin F1α, was significantly increased by treatment with simvastatin (P<0.01) and markedly repressed by the CYP8A1 inhibitor tranylcypromine (P<0.01) and the CAR antagonist clotrimazole (P<0.01) in HUVEC. The results of this study improve our understanding of the inter-individual variations in PGI2 levels. Clinical studies in humans are necessary to confirm the present in vitro results.