Cells involved in extracellular matrix remodeling after acute myocardial infarction

Abstract

Objective Evaluate the effects of VEGF165 gene transfer in the process of remodeling of the extracellular matrix after an acute myocardial infarct.Methods Wistar rats were submitted to myocardial infarction, after the ligation of the left descending artery, and the left ventricle ejection fraction was used to classify the infarcts into large and small. The animals were divided into groups of ten, according to the size of infarcted area (large or small), and received or not VEGF165 treatment. Evaluation of different markers was performed using immunohistochemistry and digital quantification. The primary antibodies used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E-cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were expressed as mean and standard error, and analyzed by ANOVA, considering statistically significant if p≤0.05.Results There was a significant increase in the expression of undifferentiated cell markers, such as fibronectin (protein present in the extracellular matrix) and CD44 (glycoprotein present in the endothelial cells). However, there was decreased expression of vimentin and PCNA, indicating a possible decrease in the process of cell proliferation after treatment with VEGF165. Markers of differentiated cells, E-cadherin (adhesion protein between myocardial cells), CD24 (protein present in the blood vessels), and alpha-1-actin (specific myocyte marker), showed higher expression in the groups submitted to gene therapy, compared to non-treated group. The value obtained by the relation between alpha-1-actin and vimentin was approximately three times higher in the groups treated with VEGF165, suggesting greater tissue differentiation.Conclusion The results demonstrated the important role of myocytes in the process of tissue remodeling, confirming that VEGF165 seems to provide a protective effect in the treatment of acute myocardial infarct.

The role of CD44 in pathological angiogenesis

“…31,127 Both blood vessel formation and CD44 expression were observed to be enhanced in rats with MI that were treated with VEGF, indicating that CD44 coordinates with VEGF to promote ischemia-induced angiogenesis. 129 These favorable findings support a role of CD44 in promoting collateral blood vessel formation after MI, possibly through mechanisms similar to those described for tumor angiogenesis. CD44 expression is also increased in isolated monocytes in coronary heart disease patients with improved vessel collateralization.…”

Adverse left ventricular remodeling by glycoprotein nonmetastatic melanoma protein B in myocardial infarction

“…One GPNMβ‐binding HSPGs in particular could be of interest: Syn‐4 is able to sense mechanical stress and activate prohypertrophic signaling responses, such as the calcineurin‐nuclear factor of activated T‐cell pathway (62). In addition, CD44, which is up‐regulated in MI (63), was identified as a receptor for GPNMB (64). Because CD44 was shown to lead to cardiomyocyte apoptosis (65), GPNMB binding to CD44 in infarcted hearts could exacerbate cardiomyocyte apoptosis, a possibility that remains to be tested in future studies.…”

Canine Placenta Recellularized Using Yolk Sac Cells with Vascular Endothelial Growth Factor

“… 32 In studies where VEGF gene therapy for recovery of infarcted cardiac areas was performed, fibronectin expression increased due to cell proliferation. 33 …”