Dynamics and implications of circulating anti-angiogenic VEGF-Ab isoform in patients with ST-elevation myocardial infarction

Angiogenesis is crucial to restore microvascular perfusion in the jeopardized myocardium in the weeks following reperfused ST-segment elevation myocardial infarction (STEMI). (VEGF)-Ab, an anti-angiogenic factor, has been identified as a regulator of vascularization; however, it has not been previously implicated in acute myocardial infarction. We sought to investigate the dynamics of circulating VEGF-Ab and its association with cardiac magnetic resonance-derived infarct size and left ventricular ejection fraction (LVEF). 50 STEMI patients and 23 controls were included. Compared with control individuals, serum VEGF-Ab was elevated in STEMI patients prior to primary percutaneous coronary intervention (PCI). Following PCI, serum VEGF-Ab increased further, reaching a maximum level at 24 h and decreased one month after reperfusion. VEGF-Ab levels at 24 h were associated with a large infarct size and inversely related to LVEF. VEGF-Ab expression was increased in myocardial infarct areas from patients with previous history of AMI. An ex vivo assay using serum from STEMI patients showed that neutralization of VEGF-Ab increased tubulogenesis. Overall, the study suggests that VEGF-Ab might play a deleterious role after AMI as an inhibitor of angiogenesis in the myocardium. Accordingly, neutralization of VEGF-Ab could represent a novel pro-angiogenic therapy for reperfusion of myocardium in STEMI.