Role of antiangiogenic VEGF-A 165 b in angiogenesis and systolic function after reperfused myocardial infarction

Angiogenesis helps to reestablish microcirculation after myocardial infarction (MI). In this study, we aimed to further understand the role of the antiangiogenic isoform vascular endothelial growth factor (VEGF)-A b after MI and to explore its potential as a coadjuvant therapy to coronary reperfusion. 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 b levels. In both experimental MI models, we assessed the functional and structural role of VEGF-A b blockade. In a cohort of 104 ST-segment elevation MI patients, circulating VEGF-A 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). In both models, circulating and myocardial VEGF-A b levels were increased 21 days after MI induction. Serum VEGF-A b levels inversely correlated with systolic function evaluated by echocardiography. VEGF-A 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 b levels correlated with depressed ejection fraction and worse outcomes. In experimental and clinical studies, higher serum VEGF-A 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 b neutralization represents a potential coadjuvant therapy to coronary reperfusion.