Dynamics and implications of circulating anti-angiogenic VEGF-A165b isoform in patients with ST-elevation myocardial infarction

<jats:title>Abstract</jats:title><jats:p>Angiogenesis is crucial to restore microvascular perfusion in the jeopardized myocardium in the weeks following reperfused ST-segment elevation myocardial infarction (STEMI). (VEGF)-A<jats:sub>165</jats:sub>b, 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-A<jats:sub>165</jats:sub>b 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-A<jats:sub>165</jats:sub>b was elevated in STEMI patients prior to primary percutaneous coronary intervention (PCI). Following PCI, serum VEGF-A<jats:sub>165</jats:sub>b increased further, reaching a maximum level at 24 h and decreased one month after reperfusion. VEGF-A<jats:sub>165</jats:sub>b levels at 24 h were associated with a large infarct size and inversely related to LVEF. VEGF-A<jats:sub>165</jats:sub>b expression was increased in myocardial infarct areas from patients with previous history of AMI. An <jats:italic>ex vivo</jats:italic> assay using serum from STEMI patients showed that neutralization of VEGF-A<jats:sub>165</jats:sub>b increased tubulogenesis. Overall, the study suggests that VEGF-A<jats:sub>165</jats:sub>b might play a deleterious role after AMI as an inhibitor of angiogenesis in the myocardium. Accordingly, neutralization of VEGF-A<jats:sub>165</jats:sub>b could represent a novel pro-angiogenic therapy for reperfusion of myocardium in STEMI.</jats:p>