Efeitos do antioxidante tempol nas alterações bioquímicas e estruturais induzidas pela metaloproteinase de matriz 2 no coração

Abstract

MMP-2 expression is elevated in many cardiovascular pathologies such as myocardial infarction and heart failure, where tissue remodeling and inflammatory responses are disturbed. Changes in ECM homeostasis can lead to cardiac dysfunction. The most analyzed MMPs in relation to cardiac dysfunction are MMP 2 and MMP-9. ROS inhibitors, as antioxidants, have been shown to reduce the expression of MMP-2 in vascular tissue. Thus, antioxidants with Tempol have great potential to act on these mechanisms. Therefore, we evaluated the activity and purity of rhMMP-2 using the zymogram and SDS-PAGE silver-stained method. The animals were divided into 4 treatment groups. Group 1: received 0.9% saline; group 2: Tempol 18 mg / kg / v.o; group 3: MMP-2 150 ng / kg / i.p; group 4: Tempol 18 mg / kg / v.o + MMP-2 150 ng / kg / i.p; for 4 weeks. At the end of the treatment, the heart was collected for quantification of collagen, quantification of ROS by fluorescence microscopy and immunofluorescence for TNFα and TGF-β. After the analysis, our results showed that rhMMP-2 was pure and active and that there was no difference in the average weight of the animals (P> 0.05). In the group treated withrhMMP-2 and Tempol, there was a decrease in the heart weight / body weight ratio, compared to the control group (P <0.05). Tempol was able to decrease collagen in the heart of animals treated with rhMMP 2. We also saw rhMMP-2 increased ROS in the heart, which was prevented by Tempol. RhMMP-2 also led to an increase in TNF-α and TGF-β in the heart, however TGF-β was reduced by Tempol. In conclusion, rhMMP-2 infusion increased cardiac ROS, which can lead to oxidative stress, with a consequent increase in TNF-α and TGF-β, which can result in a heart with a pro-fibrotic and inflammatory profile. However, Tempol was able to reduce interstitial collagen, inhibit the increase in ROS, TNF-α, TGF-β and increase catalase in the heart. Having Tempol, the potential to inhibit factors that lead to oxidative stress, inflammation and cardiac fibrosis.