Upregulation of an antiangiogenic VEGFA165b isoform in patients with acute myocardial infarction

Abstract

Background. The most prevalent manifestation of coronary artery disease is acute myocardial infarction, AMI, which is characterized by myocardial damage due to prolonged ischemia. Impaired angiogenesis or neovascularization in the infarct area and the resultant metabolic imbalance are important contributors to the transition to heart failure, the main cause of death in AMI patients in a long-term perspective. We sought to investigate the circulating levels of an anti-angiogenic VEGFA165B isoform and its association with left ventricular ejection fraction.

Methods. We investigated in 100 patients with ST segment elevation myocardial infarction and 25 age matched controls the circulating levels of VEGFA165b, its association with the presence of extensive left ventricular damage as derived from the left ventricular ejection fraction, LVEF, using cardiac magnetic resonance. We also studied whether VEGFA165b protein expression can be detected in human heart tissue of patients with previous history of AMI, and to investigate the effects of VEGFA165b blockade on angiogenesis using serum from STEMI patients in ex vivo assays.

Results. Circulating levels of VEGFA165b were significantly increased in STEMI patients compared to controls. VEGFA165b levels were inversely related to LVEF. VEGFA165b 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 VEGFA165b creased tubulogenesis of human coronary artery endothelial cells.

Conclusions. This study suggests that endogenous VEFGA165b is elevated in STEMI patients and pharmacological modulation of VEGFA165b expression and function might be a promising therapeutic strategy to accelerate angiogenesis after AMI. This study was supported by grants PIE15 00013 and PI15 00082 and CPII13 00025 from the Carlos III Health Institute, the Spanish Ministry of Economy and Competiveness, and the European Regional Development Fund FEDER.