Abstract 600: Anti-Angiogenic Effects of Circulating Exosomes From Patients With Acute Coronary Syndrome: Potential Role of miR-199a and miR-125a

Abstract

Circulating exosomes have a great impact in human health as a biomarker or as messengers in intercellular signaling. In this study we aimed to determine how miRNA profile in circulating exosomes interfere with angiogenic phenotype of endothelial cell (EC) during acute event of coronary syndrome. Exosomes were purified from serum of patients with non-ST segment elevation myocardial infarction in the acute phase (NSTEMI, n=34) during percutaneous coronary intervention. Healthy donors (n=23) were included as control. Purified exosomes were quantified and characterized by nanoparticle tracking analysis (Nanosight). Healthy EC (HUVEC) were treated for 48h with labeled exosomes (5x10 5 particles/1x10 6 cells) and tested for their angiogenic potential (migration and tube formation) and mRNA expression. Exosome miRNA profile was determined by miRNA array. Exosomes levels were markedly increased in NSTEMI (1.3x10 9 particle/ml) vs control (7.5x10 8 particle/ml; p=0.02). HUVEC treatment with healthy exosomes improve migration and tube formation compared to untreated HUVEC. Nevertheless, exosomes from NSTEMI patients, in the acute phase lack their pro-angiogenic potential (Fig A). Network analysis of exosome miRNA and HUVEC mRNA expression revealed a correlation of increased miR-199a and miR-125a expression with decrease of components involved in EC sprout and stabilization (Fig B). Circulating exosomes have an important role in the control of angiogenesis. However, in the acute phase of NSTEMI intercellular communication via exosome is modified and exert an inhibitory effect on angiogenesis. These results could contribute to the progression and outcomes of the disease.