Long-term effects for acute phase myocardial infarct VEGF(165) gene transfer cardiac extracellular matrix remodeling

Background. Cardiac remodeling is ultimately regulated by components of the extracellular matrix (ECM). We investigated the important role that growth factors play in the regulation of ECM remodeling that occurs as a consequence of myocardium damage.Methods and results. Rats were submitted to the ligation of the left anterior coronary artery and pcDNA3-vascular endothelial growth factor (VEGF)(165) was immediately injected intramyocardially in the treated group. the animals were divided into large size myocardium infarction (LMI) and small size myocardium infarction, with or without gene transfer. the plasmid-containing DNA encoding VEGF(165) was injected into the cardiac muscle and its effect was observed on the ECM components. Glycosaminoglycans were identified and quantified by agarose gel based electrophoresis and ELISA as well as immunocytochemistry to examine specific cathepsin B, heparanase, and syndecan-4 changes. the amounts of hyaluronic acid ( HA; p < 0.005), DS, chondroitin sulfate, and heparan sulfate (p < 0.001) were significantly increased in the LMI treated group in comparison to the other groups, which correlates with the decrease in the expression of heparanase. A decrease in the molecular mass of HA was found in the scar tissue of treated group.Conclusions. the data obtained strongly support the idea that changes in the ECM and its components are important determinants of cardiac remodeling after myocardium infarct and may be essential for inflammatory response and attempt to stabilize the damage and provide a compensatory mechanisms to maintain cardiac output since the ECM components analyzed are involved with angiogenesis, cell proliferation and differentiation.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundo de Apoio Docente Aluno da Universidade Federal de São Paulo (FADA/UNIFESP)Universidade Federal de São Paulo, Dept Bioquim, Disciplina Biol Mol, Dept Internal Med, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Gene Therapy, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Mol Biol, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Cardiovasc Physiol, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Vasc Surg, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Bioquim, Disciplina Biol Mol, Dept Internal Med, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Gene Therapy, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Mol Biol, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Cardiovasc Physiol, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Vasc Surg, BR-04044020 São Paulo, BrazilWeb of Scienc