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Rosiglitazone attenuates atherosclerosis in a model of insulin insufficiency independent of its metabolic effects

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journal contribution
posted on 2005-09-01, 00:00 authored by A C Calkin, J M Forbes, Craig SmithCraig Smith, M Lassila, M E Cooper, K A Jandeleit-Dahm, T J Allen
Objectives— Recent studies have demonstrated a role for thiazolidinediones in attenuating atherosclerosis. However, these studies were performed in insulin-resistant animal models in association with reductions in insulin and glucose levels. To assess the vascular effects of thiazolidinediones, independent of their metabolic effects, we observed the effect of rosiglitazone on diabetes-associated atherosclerosis in a model of insulin insufficiency.

Methods and Results— Control and diabetic apolipoprotein E–deficient mice received rosiglitazone or placebo. Diabetic mice demonstrated a 3-fold increase in plaque area, which was attenuated by rosiglitazone. There was no significant difference in glucose, insulin, or cholesterol levels between treated and untreated diabetic animals. Rosiglitazone attenuated the increase in superoxide production observed in diabetic mice. A 4-fold increase in the reverse cholesterol transport marker ABCA1 was observed in treated diabetic mice. Rosiglitazone reduced angiotensin II receptor gene expression in control and diabetic mice, and macrophage accumulation was increased in diabetic mice compared with controls and was attenuated by rosiglitazone.

Conclusions— These findings suggest peroxisome proliferator-activated receptor-γ ligands such as rosiglitazone confer vascular protection independent of their effects on metabolic control. These antiatherosclerotic effects may have important clinical ramifications not only in insulin resistance/type 2 diabetes and also in type 1 diabetes.

History

Journal

Arteriosclerosis, thrombosis, and vascular biology

Volume

25

Issue

9

Pagination

1903 - 1909

Publisher

American Heart Association

Location

Dallas, Tex.

ISSN

1079-5642

eISSN

1524-4636

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2005, American Heart Association

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