Background Rosiglitazone, an important Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, improves left ventricular hypertrophy in diet-induced hypercholesterolemic rats. However, the effects of rosiglitazone on cardiac remodelling in spontaneous hypertension rats are unclear.
Methods 20 male 8-week-old SHRs were randomly divided into two groups: one treated with oral saline (n=10) and the other treated with rosiglitazone (5 mg/kg/d) (n=10), compared with ten age-matched Wistar-Kyoto (WKY) rats as a control group. Echocardiography, immunohistochemistry, real-time RT-PCR, co-immunoprecipitation, and Western blot analysis were performed to assess the effects of rosiglitazone.
Results After 16 weeks of treatment, rosiglitazone decreased left ventricular weight (LVW) to body weight (BW) ratio (2.35±0.11 vs 2.56±0.14 mg/g, p<0.01). According to echocardiography, thickening of interventricular septum and posterior wall was prevented (2.07±0.03 vs 2.15±0.04 mm, p<0.01; 2.08±0.05 vs 2.15±0.05 mm, p<0.01, respectively) and midwall fractional shortening (MFS) was improved (23.82±0.23% vs 23.33±0.4%, p<0.01) by rosiglitazone. Rosiglitazone decreased collagen I and III mRNA expression (0.06±0.01 vs 0.18±0.01, p<0.01; 0.05±0.01 vs 0.13±0.01, p<0.01, respectively), and normalised the MMP-9/TIMP-1 ratio (1.16±0.12 vs 0.78±0.18, p<0.01). Furthermore, AP-1 activation (0.51±0.10 vs 0.71±0.09, p<0.01) and NF-κB expression (0.33±0.04 vs 0.45±0.08, p<0.01) were suppressed in treated group.
Conclusion These results suggest that treatment with rosiglitazone will improve myocardial remodelling in hypertension. Taken together, PPAR-γ agonist rosiglitazone may exert a protective effect on cardiac remodelling in SHRs by decreasing the expression of AP-1 and NF-κB.
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