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

Abstract：

AIMS:This 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. METHODS:Illumina'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. RESULTS:The 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. CONCLUSION:The nature of the pleiotropic effects may play a role in Vytorin's and Simvastatin's clinical efficacies.

journal_name

Atherosclerosis

journal_title

Atherosclerosis

authors

Sternberg Z,Chichelli T,Sternberg D,Hojnacki D,Drake A,Liu S,Hu Q,Munschauer F

doi

10.1016/j.atherosclerosis.2013.09.031

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

411-20

issue

2

eissn

0021-9150

issn

1879-1484

pii

S0021-9150(13)00590-X

journal_volume

231

pub_type

杂志文章,随机对照试验

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