title: Fluvastatin reduces soluble P-selectin and ICAM-1 levels in hypercholesterolemic patients: role of nitric oxide.
abstract: BACKGROUND
  Lipid-lowering therapy with 3-hydroxy-3-methylglutaryl-coenzymeA (HMG-CoA) reductase inhibitors reduces the incidence of atherosclerosis-related cardiovascular events. Adhesion molecules, regulating interactions between vascular and circulating cells, may play a central role in the pathogenesis of atherosclerosis and related complications. In the present report we examined the impact of the HMG-CoA reductase inhibitor fluvastatin on plasma levels of P-selectin and ICAM-1.
  
  
  METHODS
  Plasma levels of P-selectin and ICAM-1 were determined using an enzyme immunoassay in 26 patients with type IIa hypercholesterolemia randomized to treatment with either fluvastatin (80 mg/d) or placebo in a double blind fashion for 12 weeks.
  
  
  RESULTS
  Fluvastatin administration reduced either P-selectin (118 +/- 63 vs 81 +/- 36 ng/mL [-31%], P = 0.0015) or ICAM-1 (264 +/- 75 vs 228 +/- 68 ng/mL [-13.7%], P = 0.0033) levels. Fluvastatin also lowered urinary 11-dehydro-TXB2 (1396 +/- 536 vs 1009 +/- 378 pg/mg creatinine [-27%], P = 0.0015) and von Willebrand Factor levels (1456 +/- 716 vs 1203 +/- 527 U/L [-17.4%], P = 0.0275), and a direct correlation was observed between P-selectin and 11-dehydro-TXB2 levels (r = 0.588, P = 0.0033). Patients treated with fluvastatin displayed an increase in nitric oxide (NO) generation, evaluated with measurements of serum NO2-/NO3-, (4.7 +/- 1 vs 8.9 +/- 3.1) mumol/L [98%], P = 0.0046). Moreover, an inverse correlation was observed between NO2-/NO3- and P-selectin (r = -0.420; P = 0.0343), 11-dehydro-TXB2 (r = -0.511; P = 0.0106), or LDL (r = -0.742; P = 0.0002) levels.
  
  
  CONCLUSIONS
  These results may provide novel biochemical basis for the beneficial clinical effects of HMG-CoA reductase inhibitors in hypercholesterolemia.
authors.affiliation: Institute of Medical Pathology and Mediterranean Medicine, University of Messina, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Romano
authors.forename: A
authors.initials: A
authors.lastname: Mezzetti
authors.forename: C
authors.initials: C
authors.lastname: Marulli
authors.forename: G
authors.initials: G
authors.lastname: Ciabattoni
authors.forename: F
authors.initials: F
authors.lastname: Febo
authors.forename: S
authors.initials: S
authors.lastname: Di Ienno
authors.forename: S
authors.initials: S
authors.lastname: Roccaforte
authors.forename: S
authors.initials: S
authors.lastname: Vigneri
authors.forename: G
authors.initials: G
authors.lastname: Nubile
authors.forename: M
authors.initials: M
authors.lastname: Milani
authors.forename: G
authors.initials: G
authors.lastname: Davì
mesh_terms: D000328:Adult; D000368:Aged; D003404:Creatinine / Q000652:urine; D004311:Double-Blind Method; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D007211:Indoles / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D009585:Nitrogen Dioxide / Q000097:blood; D019007:P-Selectin / Q000097:blood*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D019007:P-Selectin; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D000077340:Fluvastatin; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D003404:Creatinine; D009585:Nitrogen Dioxide