Submitted on October 20, 2003
Accepted on December 15, 2003
HMG-CoA reductase inhibitor attenuates platelet adhesion in intestinal venules of hypercholesterolemic mice
Anitaben Tailor1, David J. Lefer1, and D. Neil Granger1*
1 Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA
* To whom correspondence should be addressed. E-mail: dgrang{at}lsuhsc.edu.
While the anti-inflammatory properties of statins have been extensively studied less attention has been devoted to the anti-thrombogenic effects of these drugs. We evaluated the effect of shortterm (18 hr) treatment with pravastatin (1 mg/kg) on hypercholesterolemia-induced plateletendothelial
(P/E) cell adhesion in intestinal venules. Mice were placed either on normal (ND) or cholesterol-enriched diet (HCD) for 2 weeks. Wild type mice fed a HCD exhibited significantly elevated blood serum cholesterol levels, which was 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 to 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 hypercholesterolemiainduced P/E adhesion was abolished in L-NAME-treated mice. These results indicate that: 1)
hypercholesterolemia-induced P/E adhesion is mediated by changes in the vascular wall, rather than circulating platelets, and 2) pravastatin treatment inhibits the pro-thrombogenic effects of hypercholesterolemia via an action on both endothelial cells and platelets, and 3) the protective effect of pravastatin is NO-dependent.
