Effects of statins in thrombosis and aortic lesion development in a dyslipemic rabbit model.
HMG-CoA reductase inhibitors (statins) are effective in primary and secondary prevention of coronary heart disease. The mechanism of action is mainly attributed to their plasma cholesterol lowering activity, although additional effects have been suggested. Our objective was to study whether atorvastatin and simvastatin exhibited an inhibitory effect on platelet deposition onto a triggering damaged vessel wall in addition to an antiatherosclerotic effect in the dyslipemic rabbit model. Statins were administered at identical doses of 2.5 mg/kg/day with a hyperlipidemic diet during 10 weeks. Both drugs similarly lowered total cholesterol and, moderately, triglycerides. Mural platelet deposition on damaged vessel wall placed in an ex-vivo flow perfusion system was reduced in atorvastatin treated animals (39.7+/-6.2 X 10(6) PLT/cm2) vs. controls (94.8+/-15.9 x 10(6) PLT/cm2, p <0.02). Simvastatin reduced aortic fatty streak surface coverage (31,7+/-5.3%) vs. controls (47.9+/-4.1%, p <0.005) and intimal thickening in thoracic aorta (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 streak coverage correlated positively with total cholesterol, tryglicerides and LDL-cholesterol levels in all groups. HMG-CoA reductase inhibitors similarly lowered plasma lipids but exhibited significantly different effects in the modulation of atherosclerotic development and platelet response at the tested dose. Therefore, the effect of statins on the progression and manifestation of cardiovascular disease might be also mediated by regulating platelet response to vessel injury.
Alfon
J
J
Cardiovascular Research Center, CSIC-HSCSP-UAB, Barcelona, Spain.
Pueyo Palazon
C
C
Royo
T
T
Badimon
L
L
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000069059:Atorvastatin; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000008:administration & dosage*; D006949:Hyperlipidemias / Q000097:blood* / Q000150:complications / Q000473:pathology; D008297:Male; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D011758:Pyrroles / Q000008:administration & dosage*; D011817:Rabbits; D019821:Simvastatin / Q000008:administration & dosage*; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin; D006903:Hydroxymethylglutaryl CoA Reductases