Rosiglitazone (PPARγ-agonist) attenuates atherogenesis with no effect on hyperglycaemia in a combined diabetes-atherosclerosis mouse model

Z. Levi, A. Shaish, N. Yacov, H. Levkovitz, S. Trestman, Y. Gerber, H. Cohen, A. Dvir, R. Rhachmani, M. Ravid*, D. Harats

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The administration of peroxisome proliferator-activated receptor γ (PPARγ) agonists to low-density lipoprotein (LDL)-receptor-deficient mice resulted in a reduction in the atherosclerotic lesion area in male mice, but not in female mice. The male mice also exhibited reduction in insulin resistance while the female mice did not. To further examine the relationship between PPARγ agonists, insulin resistance and atherosclerosis, we used the model of accelerated atherosclerosis in male apolipoprotein E (apoE)-deficient mice rendered diabetic by low-dose streptozotocin (STZ). Methods: Male, apoE-deficient mice (n = 48) were randomly divided into four groups. To induce diabetes, two groups received low-dose STZ and two groups served as controls. After diabetes induction, rosiglitazone (a PPARγ agonist) was administered by oral gavage to one of the diabetic and one of the non-diabetic groups. Results: Rosiglitazone reduced significantly the atherosclerotic aortic plaque area in both diabetic and non-diabetic apoE-deficient mice: 340 ± 54 vs. 201 ± 27 μmol2 (p = 0.001) in diabetic mice; 243 ± 22 vs. 158 ± 27 μmol2 (p = 0.001) in non-diabetic mice. Also, rosiglitazone reduced the correlation coefficient between plasma glucose and the degree of atherosclerosis (p < 0.0025) without affecting plasma glucose levels. The rosiglitazone-treated mice, both diabetic and non-diabetic, had higher lipid levels. Conclusions: Rosiglitazone-treated animals showed less atherosclerosis despite higher lipid levels and similar glucose levels. These data suggest a direct anti-atherogenic effect of rosiglitazone on the arterial wall.

Original languageEnglish
Pages (from-to)45-50
Number of pages6
JournalDiabetes, Obesity and Metabolism
Volume5
Issue number1
DOIs
StatePublished - Jan 2003

Keywords

  • Apolipoprotein E
  • Atherosclerosis
  • Low-dose streptozotocin
  • PPARγ
  • Rosiglitazone

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