Abstract
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 × 103 vs. 21.90 ± 11.98 × 103 μm2); 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.
Keywords
atherosclerosis - Rapamune - serum lipids - malondialdehyde - protein carbonyls -
macrophage accumulation - high cholesterol diet
