Lack of effect of simvastatin on structural remodeling in animal model of chagas cardiomyopathy

Abstract

Purpose: Chagas cardiomyopathy(CM)is characterized by a large amount of fibrosis and inflamation. As simvastatin (simva) has anti-inflamatory effects, we hypothetized that it could be an important drug in the treatment of patients with CM. The purpose was to evaluate simva in the myocardium remodeling and inflammation in an animal model of CM. Methods: 123 hamsters were divided:C-controls (25), CSimva-controls with simva 10mg/kg/day (25), Simva1-infected treated from the beginning with the same dose of simva (25), Simva2-infected treated after 4 months (24); Infectuntreated(24). Follow-up of 10 months. Interstitial collagen volume fraction (ICVF) RV and LV measured using videomorphometry and picrosirius red stained heart. Metalloproteinase 9 (MMP9) was obtained by zymography. Gene expression of TNFalpha, IFNgamma, IL10 by real time PCR and Ct. Survival by Kaplan-Meierand log rank. Comparison between groups by Kruskal-Wallis; p≤0.05. Results: Infected animals (Simva1=189±133days; Simva2=150±124;Infect=138±123) lived less than controls (C=257±80; CSimva=283±58)(p≤0.05) with no difference among infected. ICVF-RV (%) was greater in infected groups (Simva1=3.88±1.14; Simva2=2.22±0.64; Infect=4.38±0.83)than in controls (C=1.12±0.31; CSimva=2.18±0.73) (p≤0.05) with no difference among infected groups. ICVF-LV (%) was greater in infected animals (Simva1=1.83±1.01, Simva2=1.52±0.93; Infect=3.01±0.66) than in controls (C=0.68±0.31; CSimva=0.81±0.28) (p≤0.05) with no difference among infected. MMP9 was higher in infected groups (Simva1=2394±2441, Simva2=5673±4091; Infect=2392±2042) compared to controls (C=954±2332;CSimva=454±1123) (p≤0.05) with no difference among infected. TNFal-pha did not have difference among infected groups (Simva1=5.33±3.66,Simva2=4.44±2.17; Infect=6.13±3.24). IFNgamma in infected groups (Simva1=5.47±3.56, Simva2=4.46±2.08; Infect=4.21±2.09) was higher than in controls (C=8.50±2.59; CSimva=6.84±2.53) (p≤0.05) with no difference among infected. IL10 in infected animals (Simva1=9.07±4.62, Simva2=7.76±4.77;Infect=8.11±4.48) did not have difference and the values were greater than controls (C=14.11±4.40; CSimva=12.55±3.90) (p≤0.05). Conclusions: Simva did not attenuate deposition of interstitial collagen,did not change dynamics of collagen degradation,did not decrease inflammation,and did not reduce mortality.