Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery

Abstract

IntroductionExosome nanoparticles carry a composite cargo, including microRNAs (miRs). Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely unexplored. Working on clinical samples from coronary-artery by-pass graft (CABG) surgery, we investigated if: 1) exosomes containing cardiac miRs and hence putatively released by cardiac cells increase in the circulation after surgery; 2) circulating exosomes and exosomal cardiac miRs correlate with cardiac troponin (cTn), the current “gold standard” surrogate biomarker of myocardial damage.Methods and ResultsThe concentration of exosome-sized nanoparticles was determined in serial plasma samples. Cardiac-expressed (miR-1, miR-24, miR-133a/b, miR-208a/b, miR-210), non-cardiovascular (miR-122) and quality control miRs were measured in whole plasma and in plasma exosomes. Linear regression analyses were employed to establish the extent to which the circulating individual miRs, exosomes and exosomal cardiac miR correlated with cTn-I. Cardiac-expressed miRs and the nanoparticle number increased in the plasma on completion of surgery for up to 48 hours. The exosomal concentration of cardiac miRs also increased after CABG. Cardiac miRs in the whole plasma did not correlate significantly with cTn-I. By contrast cTn-I was positively correlated with the plasma exosome level and the exosomal cardiac miRs.ConclusionsThe plasma concentrations of exosomes and their cargo of cardiac miRs increased in patients undergoing CABG and were positively correlated with hs-cTnI. These data provide evidence that CABG induces the trafficking of exosomes from the heart to the peripheral circulation. Future studies are necessary to investigate the potential of circulating exosomes as clinical biomarkers in cardiac patients.

Human Pericardial Fluid Contains Exosomes Enriched with Cardiovascular-Expressed MicroRNAs and Promotes Therapeutic Angiogenesis

“…However, the characterization of the exosomes present in human biological fluids and their possible role as cell-to-cell communicators of cardiovascular relevance is still undeveloped. We have recently provided preliminary evidence that exosomes containing high levels of cardiovascular miRNAs are trafficked out of the heart to reach the peripheral blood in patients undergoing cardiac surgery using cardiopulmonary bypass 17 . This is an acute scenario that is associated with ischemia/reperfusion stress to the myocardium 17 .…”

En el Infarto agudo al miocardio los niveles plasmáticos de microvesículas extracelulares se elevan más precozmente que el aumento de la Troponina-I

“…En una publicación reciente se describe una aproximación similar a la nuestra, pero en pacientes derivados a cirugía cardiovascular. Observaron que poblaciones de MVEC de pequeño tamaño (61-90 nm y 91-120 nm) estaban elevadas en pacientes que recibieron cirugías de injertos de bypass coronario y que este efecto se correlacionaba con el incremento de Troponina cardíaca 12 .…”

“…Esta evidencia permite determinar que necesitamos mejores biomarcadores para evaluar el riesgo de esta enfermedad. Los exosomas son un tipo de microvesículas extracelulares (MVECs) de 30-100 nm, secretadas por las células, que contienen material genético y proteínas, los cuales reflejan cambios metabólicos que experimenta una cé-lula en un momento determinado [7][8][9][10][11][12][13] . Estos MVEC/ exosomas pueden circular en el plasma y la función que cumplen en el corazón, es aún un campo en desarrollo 24 .…”

The Favored Mechanism for Coping with Acute Cold Stress: Upregulation of miR-210 in Rats

“…Several studies to date have focused on cardiac disease and tumors in relation to miR-210 [11, 12]. Moreover, miR-210 is strongly linked with the hypoxia pathway [13] and upregulated in response to hypoxia-inducible factors [14].…”