title: The effect of statin therapy withdrawal on monocyte subsets.
abstract: BACKGROUND
  Three functionally distinct monocyte subsets have been identified. Statins are of undoubted effect in atherosclerosis and have numerous pleiotropic effects that contribute to their clinical success, but the effect of these drugs on monocyte subsets is unclear. We hypothesised a beneficial effect of statins on key receptor expression by monocyte subsets.
  
  
  METHODS
  Effects of temporal (2 weeks) cessation of statin therapy by 66 patients with stable coronary artery disease on monocyte subsets [CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2) and CD14+CD16++CCR2- (Mon3)], their aggregates with platelets and their expression of a number of receptors involved in inflammation (IL-6 receptor), adhesion [vascular cell adhesion molecule (VCAM)], angiogenesis [vascular endothelial growth factor (VEGF)] and repair were assessed by flow cytometry.
  
  
  RESULTS
  Statin cessation did not lead to any significant changes in absolute numbers of monocyte subsets or the degree of their aggregation with platelets. All monocyte subsets showed significant downregulation of expression of vascular endothelial factor receptor 2, Tie2 and Toll-like receptor-4 (TLR4; all changes P < 0·01). Expression of CXCR4 was only reduced in Mon1 cells (P = 0·013). There was no significant change in the expression of CD14, CD16, CCR4, IL6 receptor and VCAM (all P = NS).
  
  
  CONCLUSIONS
  Statin withdrawal does not affect counts of any of monocyte subsets, but leads to downregulation of expression of TLR4 and receptors related to angiogenesis on all subsets, as well as a decrease in density of CXCR4 expression on 'classical' Mon1. These data provide further support of pleiotropic effects of statins and their effects on monocyte pro-angiogenic and proreparative characteristics.
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Jaipersad
authors.forename: Eduard
authors.initials: E
authors.lastname: Shantsila
authors.forename: Andrew
authors.initials: A
authors.lastname: Blann
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000368:Aged; D042702:Angiopoietin-2 / Q000378:metabolism; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D009000:Monocytes / Q000187:drug effects*; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042702:Angiopoietin-2; D015703:Antigens, CD; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019947:Receptors, Interleukin-6; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A
keywords: Coronary artery disease; monocyte subsets; monocytes; statins