Objective To investigate the effects of 4-week treatment with the nonpeptide angiotensin-(1-7) analogue AVE 0991 on expression of inflammatory cytokines and remodelling induced by myocardial infarction (MI).
Methods In this study, MI was induced by left coronary artery ligation in male Sprague-Dawley (SD) rats. After 4 weeks of treatment, the heart wet weight was recorded, normalised for body weight. Left ventricle serial sections were dyed with triphenyltetrazolium chloride (TTC) stain to quantify the infarct size, with Masson's trichrome stain to quantify collagen volume fraction (CVF), and with haematoxylin-eosin (HE) stain for diameter measurement of cardiomyocytes. RT-PCR was used to investigate the synthesis of TGF-β1, TNF-α, collagen type I and III.
Results Infarct size was slightly reduced in AVE 0991 group compared to control group (42.6±3.6% vs 50.9±4.4%, p<0.01). In addition, AVE 0991 reduced MI-induced hypertrophy as quantified by diameter measurements of cardiomyocytes (vs. control group 25.49±4.37 μm vs 32.06±6.85 μm, p<0.05). The overexpression of TGF-β1 and TNF-α mRNA were inhibited by chronic AVE 0991 treatment alone (vs. control group, TGF-β1: 4.15±1.18 vs 14.23±3.84, p<0.05; TNF-α: 2.21±0.44 vs 3.87±0.55, p<0.05, respectively). AVE 0991 markedly attenuated the increase of the expression of Collagen I (1.79±0.15 vs 4.3±0.75, p<0.001) and III (3.12±0.42 vs 9.55±0.83, p<0.001) mRNA compared to control group.
Conclusion The nonpeptide angiotensin-(1-7) analogue AVE 0991 could attenuate overexpression of inflammatory cytokines and ventricular remodelling induced by myocardial infarction (MI).