Objectives: 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 (O-2(-)) production. Aim of the study was to assess whether the same phenomenon occurs in humans. Methods: Lipid profile and platelet O-2(-) production Acre 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 kith platelet production of O-2(-), 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: O-2(-) platelet generation was significantly higher (p<0.001) and significantly related to LDL cholesterol (p<0.001) in patient,, as Compared to controls. 8-keek treatment with 10 mg/day atorvastatin significantly reduced both LDL cholesterol and O-2(-) platelet production. This effect was partially related to the cholesterol-lowering, in that three days of treatment with atorvastatin significantly decreased platelet O-2(-) production, While no significant change in LDL-cholesterol levels was observed. Platelets incubated kith LDL cholesterol showed an increased O-2(-) production, which as significantly inhibited by, AACOCF3 (-78%) and DPI (-56%). Conclusions: LDL cholesterol increases platelet O-2(-) production by activating PLA2 and NADH/NADPH enzymes. Inhibition of platelet O-2(-) release by atorvastatin is partially related to cholesterol lowering effect, suggesting that other mechanisms could he responsible for the antioxidant activity of the drug.
Increased superoxide anion production by platelets in hypercholesterolemic patients / V., Sanguigni; Pignatelli, Pasquale; D., Caccese; Pulcinelli, FABIO MARIA; Lenti, Luisa; R., Magnaterra; F., Martini; R., Lauro; Violi, Francesco. - In: THROMBOSIS AND HAEMOSTASIS. - ISSN 0340-6245. - STAMPA. - 87:5(2002), pp. 796-801.
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|Titolo:||Increased superoxide anion production by platelets in hypercholesterolemic patients|
|Data di pubblicazione:||2002|
|Citazione:||Increased superoxide anion production by platelets in hypercholesterolemic patients / V., Sanguigni; Pignatelli, Pasquale; D., Caccese; Pulcinelli, FABIO MARIA; Lenti, Luisa; R., Magnaterra; F., Martini; R., Lauro; Violi, Francesco. - In: THROMBOSIS AND HAEMOSTASIS. - ISSN 0340-6245. - STAMPA. - 87:5(2002), pp. 796-801.|
|Appartiene alla tipologia:||01a Articolo in rivista|