Effect of sirolimus on the cholesterol content of aortic arch in ApoE knockout mice.
Chronic inflammatory responses involving the immune system have been implicated in the process of atherosclerosis. Sirolimus (Rapamycin, Rapamune), a potent immunosuppressant used to prevent rejection of transplanted kidneys, has also proven effective at inhibiting restenosis in humans when eluted from implanted stents. The aim of this study was to evaluate the effect of sirolimus treatment on the development of atherosclerosis in the aortic arch of apo E-/- mice fed a high-fat (Western) diet. Following 12 weeks of treatment with sirolimus (4 mg/kg/d), the cholesterol content of the arch was reduced by 36% compared to untreated control mice fed the Western diet only. Although the murine model is not comparable to the human situation, the results of this study suggest that sirolimus may exert beneficial effects on atherosclerosis in transplant patients.
Basso
M D
MD
Cardiovascular/Metabolic Diseases Department, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA.
Nambi
P
P
Adelman
S J
SJ
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics*; D002784:Cholesterol / Q000097:blood*; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D020123:Sirolimus / Q000494:pharmacology*
D001057:Apolipoproteins E; D007166:Immunosuppressive Agents; D002784:Cholesterol; D020123:Sirolimus