title: Simvastatin prevents inflammation-induced aortic stiffening and endothelial dysfunction.
abstract: OBJECTIVE
  The aim of this study was to determine whether simvastatin would protect against inflammation-induced aortic stiffening and endothelial dysfunction.
  
  
  METHODS
  Aortic pulse wave velocity (aPWV) and flow-mediated dilatation (FMD) were assessed three times, at baseline, after a 14 day administration of simvastatin or placebo and 8 h after Salmonella typhi vaccination in 50 healthy subjects.
  
  
  RESULTS
  Following vaccination there was a significant increase in aPWV in the placebo group (5.80 ± 0.87 vs. 6.21 ± 0.97 m s⁻¹, 95% CI 0.19, 0.62, P= 0.002) but not the simvastatin group (5.68 ± 0.73 vs. 5.72 ± 0.74 m s⁻¹, 95% CI -0.19, 0.27, P= 0.9; P= 0.016 for comparison). Whereas FMD response was reduced in the placebo group (6.77 ± 4.10 vs. 5.27 ± 2.88%, 95% CI -2.49, -0.52, P= 0.02) but not in the simvastatin group (7.07 ± 4.37 vs. 7.17 ± 9.94%, 95% CI -1.1, 1.3. P= 0.9, P < 0.001 for comparison). There was no difference in the systemic inflammatory response between groups following vaccination. However, there was a significant reduction in serum apolipoprotein A-I (Apo A-I) in the placebo, but not in the simvastatin, group.
  
  
  CONCLUSIONS
  Simvastatin prevents vaccination-induced aortic stiffening and endothelial dysfunction. This protective mechanism may be due to preservation of the Apo A-I lipid fraction, rather than pleiotropic anti-inflammatory effects of statins.
authors.affiliation: University of Cambridge, UK.
authors.forename: Sharon M L
authors.initials: SM
authors.lastname: Wallace
authors.forename: Kaisa M
authors.initials: KM
authors.lastname: Mäki-Petäjä
authors.forename: Joseph
authors.initials: J
authors.lastname: Cheriyan
authors.forename: Edward H
authors.initials: EH
authors.lastname: Davidson
authors.forename: Lynne
authors.initials: L
authors.lastname: Cherry
authors.forename: Carmel M
authors.initials: CM
authors.lastname: McEniery
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.forename: Ian B
authors.initials: IB
authors.lastname: Wilkinson
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Kharbanda
mesh_terms: D000328:Adult; D001011:Aorta / Q000187:drug effects* / Q000503:physiopathology; D001018:Aortic Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D001783:Blood Flow Velocity / Q000187:drug effects; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D015850:Interleukin-6 / Q000096:biosynthesis; D008055:Lipids / Q000097:blood; D008297:Male; D022562:Salmonella Vaccines; D012485:Salmonella typhi; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D008055:Lipids; D022562:Salmonella Vaccines; D019821:Simvastatin