Focus on Exosomes in Cardiovascular Research

Microparticles (MPs) and exosomes are released by cells using different mechanisms. Thus, quantitative as well as qualitative changes of both particle populations, MPs and exosomes, in patients with coronary artery disease (CAD) might reflect an altered activation status of the endothelium, platelets and leukocytes. Moreover, they might exert differential effects on the target organs, such as the endothelium. Yet, alterations in both populations have not been studied side-by-side so far. The aim of the study was to compare the impact of MPs and exosomes from healthy subjects and CAD patients on endothelial cell (EC) functional characteristics¹.

Remote ischemic preconditioning (RIPC) of the heart (i.e. brief ischemia/reperfusion cycles, subjected to a remote organ or a remote area, reduce the consecutive damage of a sustained cardiac ischemia. Although, its mechanism has been investigated thoroughly, exact interorgan transfer mechanisms of cardioprotection by RIPC are required to be further investigated. Exosomes and microvesicles/microparticles are vesicles of 30-100 nm and 100-1000 nm in diameter, respectively (collectively termed extracellular vesicles [EVs]). As EVs are able to shuttle proteins, mRNAs and microRNAs, they are ideal candidates for inter-organ communication. However, whether EVs are involved in RIPC, is unknown. The aim of this study was to investigate whether (1) IPC induces release of EVs from the heart, and (2) EVs are necessary for cardioprotection by RIPC².

Ischemia-reperfusion injury (IR) is a hallmark of cardiovascular disease and a major cause of death worldwide. Cardiac preconditioning is known to protect the heart from IR by activating several pro-survival transductional pathways. The fact that cardiac protection can also be achieved when preconditioning is applied to an organ remote from the heart (Remote Ischemic Preconditioning, RIPC) means that humoral factors are released from ischemic limbs into the circulation, potentially carrying a pro-survival message. Exosomes are nanometer-sized circulating vesicles, which mediate inter-cellular communication by ferrying diverse proteins and nucleic acids. This project studied exosomes as possible mediators of RIPC³.

High LDL-cholesterol plasma levels constitute an independent risk factor for the pathogenesis of atherothrombotic cardiovascular (CV) disease. This project aimed to study miRNAs, non-coding RNAs involved in post-transcriptional regulation of gene expression, in circulating exosomes as prognostic markers of future cardiovascular events⁴.

1. Kraenkel N, Briand S, Straessler E, Uhlemann M, Adams V, Schuler GC, Luescher TF, Moebius-Winkler S, Landmesser U. (2014) 537Microparticles and exosomes differentially impact on endothelial cell function in coronary artery disease. Cardiovasc Res 103 Suppl 1:S98. [abstract]
2. Baranyai T, Giricz Z, Varga Z, Sipos P, Paloczi K, Kittel A, Buzas E, Ferdinandy P. (2014) P435Extracellular vesicles mediate cardioprotection exerted by remote ischemic preconditioning in rats. Cardiovasc Res 103 Suppl 1:S80. [abstract]
3. Vicencio J, Zheng Y, Das D, Boi-Doku C, Sivaraman V, Hall A, Yellon D, Davidson S. (2014) 310Plasma exosomes from rats and humans protect the myocardium from ischemia-reperfusion injury. Cardiovasc Res 103 Suppl 1:S56. [abstract]
4. Suades R, Padro T, Alonso R, Mata P, Badimon L. (2014) P64Exosomal microRNA signature predicts future ischemic events in hypercholesterolemic patients. Cardiovasc Res 103 Suppl 1:S10. [abstract]