title: Modulation of adhesion molecules by cholesterol-lowering therapy in mononuclear cells from hypercholesterolemic patients.
abstract: BACKGROUND
  Cholesterol-lowering therapy has been related with several pleiotropic effects including anti-inflammatory action in vascular endothelium; however, their influence on monocyte adhesion molecules is poorly described.
  
  
  OBJECTIVE
  To investigate the effect of inhibitors of synthesis (statins) and absorption (ezetimibe) of cholesterol on expression of adhesion molecules L-selectin, PSGL-1, VLA-4, LFA-1, and Mac-1 in mononuclear cells in vivo and in vitro using THP-1 cells.
  
  
  METHODS
  The influence of simvastatin (10 mg/day), ezetimibe (10 mg/day), and their combination (10 mg each/day) on mRNA expression of adhesion molecules was analyzed in peripheral blood mononuclear cells (PBMC) from hypercholesterolemics. The effects of atorvastatin, simvastatin, and ezetimibe on mRNA and protein expression of adhesion molecules were also evaluated in THP-1 cells.
  
  
  RESULTS
  Simvastatin/ezetimibe combination, but not the monotherapies, reduced the mRNA expression of the PSGL-1, LFA-1, and Mac-1 genes in PBMC from hypercholesterolemics. Total and LDL cholesterol in serum correlated with PSGL-1 mRNA expression, whereas HDL cholesterol negatively correlated with mRNA levels of L-selectin and VLA-4 genes (P < 0.05). Plasma hsCRP was also correlated with mRNA levels of VLA-4, LFA-1, and Mac-1 (P < 0.05). Atorvastatin and simvastatin at 10 μM reduced mRNA and protein expression of L-selectin, PSGL-1, and VLA-4 in THP-1 cells (P < 0.05).
  
  
  CONCLUSIONS
  Cholesterol-lowering therapy modulates gene expression of adhesion molecules in PBMC from hypercholesterolemics and THP-1 cells. Simvastatin/ezetimibe combination gives more benefits by reducing to a larger extent the expression of adhesion molecules in mononuclear cells.
authors.affiliation: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.|Center of Molecular Biology and Pharmacogenetics, BIOREN-CEGIN, Universidad de La Frontera, Temuco, Chile.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Cerda
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Alice Cristina
authors.initials: AC
authors.lastname: Rodrigues
authors.affiliation: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Alves
authors.affiliation: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Fabiana Dalla Vecchia
authors.initials: FD
authors.lastname: Genvigir
authors.affiliation: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Cristina Moreno
authors.initials: CM
authors.lastname: Fajardo
authors.affiliation: University Hospital, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Egidio Lima
authors.initials: EL
authors.lastname: Dorea
authors.affiliation: University Hospital, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Gusukuma
authors.affiliation: University Hospital, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Gelba Almeida
authors.initials: GA
authors.lastname: Pinto
authors.affiliation: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Mario Hiroyuki
authors.initials: MH
authors.lastname: Hirata
authors.affiliation: Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Rosario Dominguez Crespo
authors.initials: RD
authors.lastname: Hirata
mesh_terms: D000368:Aged; D000069059:Atorvastatin / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D000069438:Ezetimibe / Q000627:therapeutic use*; D000069499:Ezetimibe, Simvastatin Drug Combination / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D019821:Simvastatin / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000069499:Ezetimibe, Simvastatin Drug Combination; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D000069059:Atorvastatin; D019821:Simvastatin; D000069438:Ezetimibe
keywords: Adhesion molecules; Cholesterol-lowering; Ezetimibe; Hypercholesterolemia; Statins