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Thromb Haemost 2002; 87(05): 796-801
DOI: 10.1055/s-0037-1613086
Review Article
Schattauer GmbH

Increased Superoxide Anion Production by Platelets in Hypercholesterolemic Patients

Valerio Sanguigni
1   Department of Internal Medicine, University “Tor Vergata”, Rome, Italy
,
Pasquale Pignatelli
2   Department of Experimental Medicine and Pathology, University “La Sapienza”, Rome, Italy
,
Daniela Caccese
,
Fabio M. Pulcinelli
2   Department of Experimental Medicine and Pathology, University “La Sapienza”, Rome, Italy
,
Luisa Lenti
2   Department of Experimental Medicine and Pathology, University “La Sapienza”, Rome, Italy
,
Roberta Magnaterra
,
Francesca Martini
2   Department of Experimental Medicine and Pathology, University “La Sapienza”, Rome, Italy
,
Renato Lauro
1   Department of Internal Medicine, University “Tor Vergata”, Rome, Italy
,
Francesco Violi
2   Department of Experimental Medicine and Pathology, University “La Sapienza”, Rome, Italy
› Author Affiliations
Further Information

Publication History

Received 14 November 2001

Accepted after revision 14 January 2002

Publication Date:
11 December 2017 (online)

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Summary

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 (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 sexmatched 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 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.

Condensed Abstract

Platelets O2 − production is enhanced in patients with hypercholesterolemia and significantly correlated with LDL cholesterol. Treatment of hypercholesterolemic patients with atorvastatin inhibited platelet O2 − production through a mechanism which is partially dependent on its cholesterol lowering effect, indicating a non-lipid lowering antioxidant effect. In vitro incubation of platelets with LDL cholesterol enhanced O2 − production which was inhibited by inhibitors of phospholipase A2 and NADH/NADPH enzymes, suggesting that these pathways contribute to LDL-induced platelet O2– production.

Keywords

Hypercholesterolemia - arachidonic acid - platelets - superoxide anion - atorvastatin
 

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