The effects of PPARγ agonist rosiglitazone on neointimal hyperplasia in rabbit carotid anastomosis model

Abstract

BackgroundNeointimal hyperplasia involving smooth muscle cell (SMC) proliferation, migration and extracellular matrix (ECM) degradation is an important component of atherosclerosis. It develops as a response to vascular injury after balloon angioplasty and vascular graft placement. Matrix metalloproteinases (MMPs) induce SMC proliferation, migration and contribute to intimal hyperplasia by degrading ECM. PPARγ agonists inhibit SMC proliferation, migration and lesion formation. In this study, we aimed to investigate the effects of PPARγ agonist rosiglitazone on neointimal hyperplasia and gelatinase (MMP-2 and MMP-9) expressions in rabbit carotid anastomosis model.MethodsNew Zealand white rabbits (n = 13, 2.7–3.2 kg) were divided into placebo and treatment groups. Right carotid artery (CA) was transected and both ends were anastomosed. Treatment group (n = 6) received rosiglitazone (3 mg/kg/day/p.o.) and placebo group (n = 7) received PBS (phosphate buffered saline, 2.5 ml/kg/day/p.o.) for 4 weeks postoperatively. After the sacrification, right and left CAs were isolated. Morphometric analyses and immunohistochemical examinations for gelatinases were performed.ResultsIntimal area (0.055 ± 0.005 control vs 0.291 ± 0.020 μm2 anastomosed, p < 0,05) and index (0.117 ± 0.002 control vs 0.574 ± 0.013 anastomosed, p < 0,01) significantly increased in anastomosed arteries compared to control arteries from placebo group. However, in rosiglitazone-treated group, intimal area (0.291 ± 0.020 PBS vs 0.143 ± 0.027 rosiglitazone, p < 0,05) and index (0.574 ± 0.013 PBS vs 0.263 ± 0.0078 rosiglitazone, p < 0,01) significantly decreased. Furthermore, gelatinase immunopositivity was found to have significantly increased in anastomosed arteries from placebo group and decreased with rosiglitazone treatment.ConclusionsThese results suggest that rosiglitazone may prevent neointimal hyperplasia, which is the most important factor involved in late graft failure, by inhibiting gelatinase enzyme expression.

Allium sativum Compared to Cilostazol as an Inhibitor of Myointimal Hyperplasia

“…The animals were euthanized with a lethal dose of an anesthetic (150 mg.kg -1 pentobarbital [19,20] . The right external iliac artery, which received balloon injury due to the surgical procedure, was collected transabdominally.…”

“…The sample size was arbitrated within thirty rabbits, 10 (ten) for each group studied; since in the literature there are studies that prove acceptable statistical results with fewer animals in the experiment with similar animal model [5,15,17,20] .…”

“…ANOVA tests were used (one-way and two-way) [20] with confirmatory testing: Tukey (multicomparative) for quantitative data and the Chi-square test for qualitative data, both with two-tailed hypothesis. Where the two-way analysis of variance test was used for continuous temporal variables and the one-way test was used for transverse continuous variables.…”

“…Where the two-way analysis of variance test was used for continuous temporal variables and the one-way test was used for transverse continuous variables. Furthermore, the Tukey test was used for quantitative data (continuous variables) because there was more than one group with different drugs [20] , whereas the χ 2 test was used for qualitative data (nominal categorical variables).…”

Pharmacological Inhibition of Vanin Activity Attenuates Transplant Vasculopathy in Rat Aortic Allografts

“…22,23 To investigate if inhibition of vanin activity results in higher expression levels of PPARγ, aortas harvested at week 4 were stained for PPARγ expression. Although in fatty tissue, a high nuclear PPARγ expression was observed (positive control; Figure 5A), no PPARγ expression could be detected in the NI, neither in the presence nor absence of RR6 ( Figure 5B).…”