Quantitative and qualitative pleiotropic differences between Simvastatin single and Vytorin combination therapy in hypercholesterolemic subjects

- We compared Vytorin and Simvastatin pleiotropic effects in patients with hypercholesterolemia.
- A larger number of pleiotropic genes was altered post-Vytorin than post-Simvastatin therapy.
- The nature of the pleiotropic genes differed between Vytorin and Simvastatin.
- Differences in the Pleiotropic genes may contribute to the clinical efficacy of the two drugs.

AimsThis cross-sectional study tested the hypothesis that treatment with the combination of Ezetimibe/Simvastatin (Vytorin) leads to broader changes in the expression levels of immunomodulatory genes as compared to Simvastatin monotherapy.MethodsIllumina's GenomeStudio gene expression module was used to compare gene profiles of Vytorin and Simvastatin in the peripheral blood mononuclear cells of 20 hypercholesterolemic subjects.ResultsThe characteristics of the immunomodulatory genes, which were altered by Vytorin, differed from those genes which were altered by Simvastatin. Vytorin mostly altered the expression levels of genes related to inflammation/oxidative stress; it downregulated the NF-KappaB and upregulated the expression of anti-inflammatory cytokine, IL-10, and anti-oxidant enzymes, GPX1 and SOD2, but also upregulated the expression levels of genes involved in cellular activation, adhesion, and coagulation cascade, including VWF, F7, PF4, PF4V1 SELP, ITGB3, ITGB5.Simvastatin mostly altered the expression levels of genes related to cellular apoptosis/proliferation. It upregulated the expression levels of apoptosis-related genes APAF1, BAX, IER3, and CSF1R, and downregulated the expression levels of genes related to cellular proliferation, including PTN and CD69. Treatment with Vytorin combination therapy modulated lipid profile and serum levels of the C-reactive protein more effectively, than treatment with Simvastatin monotherapy.ConclusionThe nature of the pleiotropic effects may play a role in Vytorin's and Simvastatin's clinical efficacies.