Role of antiangiogenic VEGF-A165b in angiogenesis and systolic function after reperfused myocardial infarction

Introduction and objectives: Angiogenesis helps to reestablish microcirculation after myocardial infarction (ML). In this study, we aimed to further understand the role of the antiangiogenic isoform vascular endothelial growth factor (VEGF)-A(165)b after ML and to explore its potential as a coadjuvant therapy to coronary reperfusion. Methods: Two mice MI models were formed: a) permanent coronary ligation (nonreperfused MI); b) transient 45-minute coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction. We determined serum and myocardial VEGF-A(165)b levels. In both experimental MI models, we assessed the functional and structural role of VEGF-A(165)b blockade. In a cohort of 104 ST-segment elevation MI patients, circulating VEGF-A(165)b levels were correlated with cardiovascular magnetic resonance-derived left ventricular ejection fraction at 6 months and with the occurrence of adverse events (death, heart failure, and/or reinfarction). Results: In both models, circulating and myocardial VEGF-A(165)b levels were increased 21 days after MI induction. Serum VEGF-A(165)b levels inversely correlated with systolic function evaluated by echocardiography. VEGF-A(165)b blockade increased capillary density, reduced infarct size, and enhanced left ventricular function in reperfused, but not in nonreperfused, MI experiments. In patients, higher VEGF-A(165)b levels correlated with depressed ejection fraction and worse outcomes. Conclusion: In experimental and clinical studies, higher serum VEGF-A(165)b levels are associated with worse systolic function. Their blockade enhances neoangiogenesis, reduces infarct size, and increases ejection fraction in reperfused, but not in nonreperfused, MI experiments. Therefore, VEGF-A(165)b neutralization represents a potential coadjuvant therapy to coronary reperfusion. (C) 2020 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.