Abstract | OBJECTIVES: We sought to investigate the anti-atherogenic effects of a selective peroxisomal proliferator-activated receptor-gamma ( PPAR-gamma) agonist and simvastatin, as well as their combination, over time, in a rabbit model of experimental atherosclerosis. BACKGROUND: The PPARs are nuclear transcription factors that control a variety of cellular functions, with the potential effects required to induce plaque regression and stabilization. METHODS:
Atherosclerosis was induced in rabbits (n = 37) by the combination of double-balloon injury and a nine-month high- cholesterol (HC) diet. The rabbits were randomized into a continued HC diet, a normal chow (NC) diet, NC plus simvastatin, NC plus PPAR-gamma agonist, and NC plus simvastatin plus PPAR-gamma agonist. All rabbits underwent magnetic resonance imaging (MRI) at randomization and after six months of treatment and were then sacrificed for histopathologic study. RESULTS: All groups had a similar vessel wall area by MRI (8.45 +/- 0.65 mm(2), p = NS between groups) at randomization. Significant progression was seen in the HC diet group (15 +/- 4%, p < 0.01). In the NC and NC plus PPAR-gamma agonist groups, progression was abolished (-2.5 +/- 3% and -4.5 +/- 5%, respectively; p = NS). The NC plus simvastatin and NC plus simvastatin plus PPAR-gamma agonist groups had significant plaque regression (-12 +/- 4% [p < 0.05] and -22 +/- 4% [p < 0.01], respectively). Regression was independent of plasma lipid levels. All NC groups had similar lipid profiles at the end of treatment. Histopathologic analysis of the NC groups showed a decreased macrophage content and matrix metalloproteinase activity and an increased smooth muscle cell/ collagen content of lesions. CONCLUSIONS:
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Authors | Roberto Corti, Julio I Osende, John T Fallon, Valentin Fuster, Gabor Mizsei, Hani Jneid, Samuel D Wright, William F Chaplin, Juan J Badimon |
Journal | Journal of the American College of Cardiology
(J Am Coll Cardiol)
Vol. 43
Issue 3
Pg. 464-73
(Feb 04 2004)
ISSN: 0735-1097 [Print] United States |
PMID | 15013132
(Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Anti-Inflammatory Agents
- Hypolipidemic Agents
- Receptors, Cytoplasmic and Nuclear
- Transcription Factors
- Simvastatin
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Topics |
- Animals
- Anti-Inflammatory Agents
(therapeutic use)
- Arteriosclerosis
(diagnosis, drug therapy)
- Drug Synergism
- Hypolipidemic Agents
(therapeutic use)
- Magnetic Resonance Imaging
- Male
- Models, Animal
- Rabbits
- Receptors, Cytoplasmic and Nuclear
(agonists)
- Remission Induction
- Simvastatin
(therapeutic use)
- Transcription Factors
(agonists)
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