Long-term effects for acute phase myocardial infarct VEGF165 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.


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.
Mataveli
Fabio D'Aguiar
FD
Department of Internal Medicine, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil. fabio.mataveli@gmail.com
Han
Sang Won
SW
Nader
Helena Bonciani
HB
Mendes
Aline
A
Kanishiro
Rose
R
Tucci
Paulo
P
Lopes
Antonio Carlos
AC
Baptista-Silva
Jose Carlos Costa
JC
Marolla
Ana Paula Cleto
AP
de Carvalho
Leonardo Pinto
LP
Denapoli
Priscila Martins Andrade
PM
Pinhal
Maria Aparecida da Silva
MA
D000818:Animals; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D015316:Genetic Therapy; D006025:Glycosaminoglycans / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007273:Injections, Intramuscular; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000235:genetics
D006025:Glycosaminoglycans; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A