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This Article Full Text Full Text (PDF) All Versions of this Article: 286/4/H1402    most recent 00993.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Tailor, A. Articles by Granger, D. N. Search for Related Content PubMed PubMed Citation Articles by Tailor, A. Articles by Granger, D. N.

HMG-CoA reductase inhibitor attenuates platelet adhesion in intestinal venules of hypercholesterolemic mice

Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3982

Submitted 20 October 2003 ; accepted in final form 15 December 2003

Whereas the anti-inflammatory properties of statins have been extensively studied, less attention has been devoted to the antithrombogenic effects of these drugs. We evaluated the effect of short-term (18 h) treatment with pravastatin (1 mg/kg) on hypercholesterolemia-induced platelet-endothelial (P/E) cell adhesion in intestinal venules. Mice were placed on either a normal diet (ND) or cholesterol-enriched diet (HCD) for 2 wk. Wild-type mice fed a HCD exhibited significantly elevated blood serum cholesterol levels, which were unaltered by pravastatin treatment. ND or HCD platelets were isolated, fluorescently labeled, and administered to either ND or HCD recipients. Intravital videomicroscopy was used to quantify transient (saltation) and firm adhesion of platelets. HCD mice receiving platelets from either ND or HCD mice exhibited increased P/E cell interactions compared with ND mice receiving platelets from ND or HCD mice. P/E adhesion was dramatically reduced when platelets from donor mice, recipient mice, or both were treated with pravastatin. The protective effect of pravastatin in hypercholesterolemia-induced P/E cell adhesion was abolished in N^G-nitro-L-arginine methyl ester-treated mice. These results indicate that 1) hypercholesterolemia-induced P/E cell adhesion is mediated by changes in the vascular wall rather than circulating platelets; 2) pravastatin treatment inhibits the prothrombogenic effects of hypercholesterolemia via an action on both endothelial cells and platelets; and 3) the protective effect of pravastatin is nitric oxide dependent.

thrombosis; statins; nitric oxide; microcirculation; inflammation