Antioxidant Tempol Attenuates Matrix Metalloproteinase 2 (MMP-2) Induced Cardiac Remodeling In Mice

Antioxidant Tempol Attenuates Matrix Metalloproteinase 2 (MMP-2) Induced Cardiac Remodeling In Mice

• Autor
• Pricila Rodrigues Gonçalves
• Co-autores
• Thayná Matos da Cunha Catete , David Silva da Costa , Wictória Farias Dias , Stefanne de Cássia Pereira da Silva , Herald Sousa Reis , Manoel Benedito Sousa Cantão , Sávio Monteiro Santos , Keuri Eleutério Rodrigues , Agenor Valadares Santos , Marta Chagas Monteiro , Raquel Fernanda Gerlach , Alejandro Ferraz do Prado
• Resumo

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  Introduction: Matrix metalloproteinase 2 increases in heart failure, where this protease induces several biochemical and structural alteration changes through a mechanism not yet elucidated. Recently has been shown that MMP-2 can increase reactive oxygen species by activating oxidating pathways. Thus, this study hypothesis that MMP-2 induces cardiac remodeling by increasing ROS. This study aims to evaluate the effects of the antioxidant tempol (an agent mimetic of the superoxide dismutase) on the biochemical and structural changes in mice's heart after four weeks of systemic administration of recombinant MMP-2. Methods: MMP-2 was expressed in bacteria E. coli, and the protein was purified in column chromatography. We evaluated rhMMP-2 activity and purity using the zymogram and SDS-PAGE silver-stained method. C57BL / 6 mice [wild type (Wt)], No. 6175230518 CEUA, young adults (7 weeks), 25.3 g, were divided into four groups. Group 1: received 0.9% saline; Group 2: Tempol 18 mg/kg/v.o; Group 3: MMP-2 150 ng/g of animal/i.p; Group 4: Tempol 18 mg kg/ v.o + MMP-2 150 ng/g of animal/i.p; for 4 weeks. The heart was collected to quantify morphological changes by hematoxylin and eosin. ROS, expression of TNF?, and TGF-? were done by immunofluorescence. The catalase activity was made by spectrophotometry.  Results: rhMMP-2 was pure and active. There was no difference in the bodyweight of the animals (P> 0.05). Administration of MMP-2 increased ROS, catalase activity, TNF-?, and TGF-? expression in the heart (P<0,05), which was prevented by Tempol (P<0,05). No difference was found in the left ventricle's thickness and the septum between the groups (P>0,05). However, the MMP-2 administration increased the area of ??the left ventricle (p<0,05), which was reduced with the treatment with tempol (p<0,05). Conclusion: Antioxidant tempol attenuates the structural and biochemical alteration induced by MMP-2 administration, suggesting the participation of TNF-?, TGF-?, and ROS in cardiac remodeling.

• Palavras-chave
• MMP-2, cardiac changes, oxidative stress, TNF-? TGF-?
• Modalidade
• Pôster
• Área Temática
• Inflamação e doenças vasculares