Effects of rapamycin on the arterial inflammatory response in atherosclerotic plaques in Apo-E knockout mice

J. J. Naoum, K. J. Woodside, S. Zhang, P. G. Rychahou, G. C. Hunter

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Because of its antiproliferative properties and its known effects on plasma lipids, we evaluated the mechanisms underlying the effect of rapamycin (RPM) on endothelial nitric oxide synthase (eNOS) and matrix metalloproteinases in Apo-E knockout mice. Apo-E-/- mice fed a high-cholesterol diet were given RPM (3 mg/kg per day intraperitoneally) or no treatment for 10 weeks (n = 8 each). Blood was drawn for serum lipid analysis. Protein was extracted from the abdominal aortas for Western immunoblotting and zymography. Cellular localization was assessed by histology and immunohistochemistry. The data, expressed as mean ± SEM, were compared by Student's t test or analysis of variance (ANOVA). Lipid levels at 10 weeks were similar in both groups except for higher triglyceride levels in RPM-treated animals. RPM-treated mice expressed greater amounts of eNOS and p-eNOS compared with controls (P <. 05). Akt, p-Akt, Caveolin-1, and p-Caveolin-1 were not significantly affected by RPM treatment. RPM treatment was associated with increased activation of pro-MMP-9, a significant decrease in MMP-2 tissue levels, and corresponding increases in TIMP-2 and TIMP-3 expression. The increased expression and phosphorylation of eNOS with RPM appears to be regulated by mechanisms other than Akt or Caveolin-1. Alterations in eNOS expression, in addition to changes in MMP/TIMP ratios and MMP-2 and MMP-9 activation, may partially explain the changes observed in the aorta of treated Apo-E-/- mice induced by RPM.

Original languageEnglish
Pages (from-to)1880-1884
Number of pages5
JournalTransplantation Proceedings
Volume37
Issue number4
DOIs
StatePublished - May 2005

Bibliographical note

Funding Information:
Supported by the Sealy Center for Aging and the American Heart Association.

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Fingerprint

Dive into the research topics of 'Effects of rapamycin on the arterial inflammatory response in atherosclerotic plaques in Apo-E knockout mice'. Together they form a unique fingerprint.

Cite this