title: Increased superoxide anion production by platelets in hypercholesterolemic patients.
abstract: OBJECTIVE
  The purpose of this study was to investigate the relationship between hypercholesterolemia and superoxide anion production.
  
  
  BACKGROUND
  Experimental studies demonstrated that hypercholesterolemia is associated with enhanced cellular superoxide anion (O2-) production. Aim of the study was to assess whether the same phenomenon occurs in humans.
  
  
  METHODS
  Lipid profile and platelet O2- production were measured in 28 patients with hypercholesterolemia, compared with 25 age- and sex-matched healthy subjects, and in 21 out of the 28 patients after 8-week treatment with 10 mg/day atorvastatin (a HMGCoA reductase inhibitor). In order to assess the mechanism by which LDL cholesterol interferes with platelet production of O2-, human platelets were incubated with LDL cholesterol in the presence of either an inhibitor of the phospholipaseA2 enzyme, AACOCF3, or an inhibitor of NADH/NADPH oxidases, DPI.
  
  
  RESULTS
  O2- platelet generation was significantly higher (p <0.001) and significantly related to LDL cholesterol (p <0.001 ) in patients as compared to controls. 8-week treatment with 10 mg/day atorvastatin significantly reduced both LDL cholesterol and O2- platelet production. This effect was partially related to the cholesterol-lowering, in that three days of treatment with atorvastatin significantly decreased platelet O2- production, while no significant change in LDL-cholesterol levels was observed. Platelets incubated with LDL cholesterol showed an increased O2- production, which was significantly inhibited by AACOCF3 (-78%) and DPI (-56%).
  
  
  CONCLUSIONS
  LDL cholesterol increases platelet O2- production by activating PLA2 and NADH/NADPH enzymes. Inhibition of platelet O2- release by atorvastatin is partially related to cholesterol lowering effect, suggesting that other mechanisms could be responsible for the antioxidant activity of the drug.
authors.affiliation: Department of Internal Medicine, University Tor Vergata, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Sanguigni
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pignatelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Caccese
authors.forename: Fabio M
authors.initials: FM
authors.lastname: Pulcinelli
authors.forename: Luisa
authors.initials: L
authors.lastname: Lenti
authors.forename: Roberta
authors.initials: R
authors.lastname: Magnaterra
authors.forename: Francesca
authors.initials: F
authors.lastname: Martini
authors.forename: Renato
authors.initials: R
authors.lastname: Lauro
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use; D016718:Arachidonic Acid / Q000097:blood; D000069059:Atorvastatin; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood / Q000494:pharmacology; D003430:Cross-Sectional Studies; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D013481:Superoxides / Q000097:blood*; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D011758:Pyrroles; D014280:Triglycerides; D013481:Superoxides; D016718:Arachidonic Acid; D002784:Cholesterol; D000069059:Atorvastatin