Long-term effects for acute phase myocardial infarct VEGF165 gene transfer cardiac extracellular matrix remodeling

• Published in: Growth factors (Chur, Switzerland) Vol. 27; no. 1; pp. 22 - 31
• Main Authors: Mataveli, Fabio D'Aguiar, Han, Sang Won, Nader, Helena Bonciani, Mendes, Aline, Kanishiro, Rose, Tucci, Paulo, Lopes, Antonio Carlos, Baptista-Silva, Jose Carlos Costa, Marolla, Ana Paula Cleto, Pinto de Carvalho, Leonardo, Denapoli, Priscila Martins Andrade, Aparecida da Silva Pinhal, Maria
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01-01-2009; Taylor & Francis
• Subjects: Animals; Extracellular Matrix - chemistry; Extracellular Matrix - metabolism; Female; Genetic Therapy; Glycosaminoglycans - analysis; Glycosaminoglycans - metabolism; Humans; Injections, Intramuscular; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial Infarction - therapy; Myocardium - metabolism; Myocardium - pathology; Rats; Rats, Wistar; Treatment Outcome; Vascular Endothelial Growth Factor A - administration & dosage; Vascular Endothelial Growth Factor A - genetics
• ISSN: 0897-7194; 1029-2292
• DOI: 10.1080/08977190802574765

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 VEGF165 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.