Effects of statins in thrombosis and aortic lesion development in a dyslipemic rabbit model

HMG-CoA reductase inhibitors(statins) are effective in primary and secondar y prevention of coronary heart disease. The mechanism of action is mainly a ttributed to their plasma cholesterol lowering activity, although additiona l effects have been suggested. Our objective was to study whether atorvasta tin and simvastatin exhibited an inhibitory effect on platelet deposition o nto a triggering damaged vessel wall in addition to an antiatherosclerotic effect in the dyslipemic rabbit model. Statins were administered at identic al doses of 2.5 mg/kg/day with a hyperlipidemic diet during 10 weeks. Both drugs similarly lowered total cholesterol and, moderately, triglycerides. M ural platelet deposition on damaged vessel wall placed in an ex-vivo Bow pe rfusion system was reduced in atorvastatin treated animals (39.7 +/- 6.2 x 10(6) PLT/cm(2)) vs. controls (94.8 +/- 15.8 x 10(6) PLT/cm(2), p <0.02). S imvastatin reduced aortic fatty streak surface coverage (31,7 +/- 5.356) vs . controls (47.9 +/- 4.1%, p <0.005) and intimal thickening in thoracic aor ta (0.15 +/- 0.05 intima to total area ratio in simvastatin treated animals vs. 0.36 +/- 0.03 in control animals, p <0.05). Atherosclerotic fatty stre ak coverage correlated positively with total cholesterol, tryglicerides and LDL-cholesterol levels in all groups. HMG-CoA reductase inhibitors similar ly lowered plasma lipids but exhibited significantly different effects in t he modulation of atherosclerotic development and platelet response at the t ested dose. Therefore, the effect of statins on the progression and manifes tation of cardiovascular disease might be also mediated by regulating plate let response to vessel injury.