title: Quantitative and qualitative pleiotropic differences between Simvastatin single and Vytorin combination therapy in hypercholesterolemic subjects.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  The nature of the pleiotropic effects may play a role in Vytorin's and Simvastatin's clinical efficacies.
authors.affiliation: Department of Neurology, Stroke Center, Buffalo Medical Center, Buffalo, NY, USA. Electronic address: zs2@buffalo.edu.
authors.forename: Zohara
authors.initials: Z
authors.lastname: Sternberg
authors.forename: Trevor
authors.initials: T
authors.lastname: Chichelli
authors.forename: Daniel
authors.initials: D
authors.lastname: Sternberg
authors.forename: David
authors.initials: D
authors.lastname: Hojnacki
authors.forename: Allison
authors.initials: A
authors.lastname: Drake
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hu
authors.forename: Frederick
authors.initials: F
authors.lastname: Munschauer
mesh_terms: D000328:Adult; D001384:Azetidines / Q000008:administration & dosage*; D002097:C-Reactive Protein / Q000378:metabolism; D018592:Cross-Over Studies; D003430:Cross-Sectional Studies; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000235:genetics; D007107:Immune System / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010973:Platelet Adhesiveness / Q000187:drug effects; D019821:Simvastatin / Q000008:administration & dosage*; D013927:Thrombosis / Q000188:drug therapy / Q000235:genetics
chemical_list: D001384:Azetidines; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D002097:C-Reactive Protein; D019821:Simvastatin
keywords: ACE; ACS; ALT; ARB; AST; BP; CHD; CIMT; CRP; Dyslipidemia; Ezetimibe; HDL; IL; Inflammation; LDL; Microarray; Mononuclear cells; NFk-B; PBMCs; Platelet adhesion; ROS; Statin; TC; TNF; TRG; Thrombosis; VWF; acute coronary syndrome; alanine aminotransferase; angiotensin receptor blockers; angiotensin-converting enzyme; aspartate aminotransferase; blood pressure; c-reactive protein; carotid intima-media thickness; coronary heart disease; high-density lipoprotein cholesterol; interleukin; low-density lipoprotein cholesterol; nuclear factor kappaB; peripheral blood mononuclear cells; reactive oxygen species; total cholesterol; triglyceride; tumor necrosis factor; von Willebrand factor