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Title: Oral rapamycin attenuates atherosclerosis without affecting the arterial responsiveness of resistance vessels in apolipoprotein E-deficient mice
metadata.dcterms.creator: Gadioli, Adriana Lários Nobrega
Nogueira, Breno Valentim
Arruda, R. M. P.
Pereira, Raquel Binda
Meyrelles, Silvana dos Santos
Arruda, J. A.
Vasquez, Elisardo C. (Elisardo Corral)
metadata.dcterms.subject: Sirolimo;Aterosclerose;Apolipoproteína E;Resistência vascular;Sirolimus;Atherosclerosis;Vascular responsiveness;Apolipoprotein E;Mice;Rapamycin
metadata.dcterms.issued: Dec-2009
metadata.dcterms.abstract: The objective of the present study was to assess the effects of the immunosuppressant rapamycin (Rapamune®, Sirolimus) on both resistance vessel responsiveness and atherosclerosis in apolipoprotein E-deficient 8-week-old male mice fed a normal rodent diet. Norepinephrine (NE)-induced vasoconstriction, acetylcholine (ACh)- and sodium nitroprusside (SNP)-induced vasorelaxation of isolated mesenteric bed, and atherosclerotic lesions were evaluated. After 12 weeks of orally administered rapamycin (5 mg·kg-1·day-1, N = 9) and compared with untreated (control, N = 9) animals, rapamycin treatment did not modify either NE-induced vasoconstriction (maximal response: 114 ± 4 vs 124 ± 10 mmHg, respectively) or ACh- (maximal response: 51 ± 8 vs 53 ± 5%, respectively) and SNP-induced vasorelaxation (maximal response: 73 ± 6 vs 74 ± 6%, respectively) of the isolated vascular mesenteric bed. Despite increased total cholesterol in treated mice (982 ± 59 vs 722 ± 49 mg/dL, P < 0.01), lipid deposition on the aorta wall vessel was significantly less in rapamycin-treated animals (37 ± 12 vs 68 ± 8 µm2 x 103). These results indicate that orally administered rapamycin is effective in attenuating the progression of atherosclerotic plaque without affecting the responsiveness of resistance vessels, supporting the idea that this immunosuppressant agent might be of potential benefit against atherosclerosis in patients undergoing therapy.
ISSN: 1678-4510
Appears in Collections:PPGCF - Artigos publicados em periódicos

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