Rapamune does not attenuate high cholesterol-induced atherosclerosis in rabbits

Solid-organ transplant recipients are prone to develop atherosclerosis. The objectives of this study were to investigate the effects of Rapamune (Wyeth Canada, Saint-Larent, QC, Canada) on the rabbit model of atherosclerosis. The rabbits were assigned to four groups: group I, regular diet (control); group II, 1% cholesterol diet; group III, control with Rapamune (1 mg/kg/d orally); and group IV, high cholesterol diet with Rapamune. Blood samples for serum lipids (triglycerides [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C]), as well as malondialdehyde, and protein carbonyls, the indices of oxidative stress were collected at the end of 2 months on the respective diet regimen. Aortic tissue for atherosclerotic changes were also collected for oxidative stress indices were also collected. Rapamune reduced serum levels of TG, TC, LDL-C, and HDL-C. Rapamune elevated the oxidative stress in rabbits on high cholesterol diet. Rapamune did not attenuate extent of atherosclerosis (group II vs. group IV, 45.00 ± 12.00 vs. 57.28 ± 2.99%); intimal thickness (group II vs. group IV, 32.38 ± 7.14 × 10(3) vs. 21.90 ± 11.98 × 10(3) μm(2)); intimal/medial ratio (group II vs. group IV, 0.50 ± 0.06 vs. 0.35 ± 0.06); and macrophage accumulation (group II vs. group IV, 69.72 ± 5.02 vs. 61.52 ± 8.94%) in the intima of rabbits on high cholesterol diet. The data suggest that (1) Rapamune increased the oxidative stress in rabbits on high cholesterol diet and (2) Rapamune did not attenuate the hypercholesterolemic atherosclerosis in the rabbit model.