Impaired endothelial function and integrity are a hallmark of atherosclerosis, strongly related to inflammatory mechanisms [1]. Exercise training improves endothelial function and may limit inflammatory load in patients with coronary disease [2]. Extracellular vesicles (EV) mediate inter-cellular communication and can regulate endothelial cell function as well as indicate endothelial cell stress and activation [3-5]. Several species of EV have been identified, including large, medium-size and small EV (lEV, mEV, sEV) which roughly represent apoptotic bodies, shed microvesicles and exosomes, respectively [6, 7]. sEV and mEV differ with respect to their intracellular origin and mechanism of release, as well as their size and molecular composition [4, 6]. They might therefore show different release and uptake kinetics, as well as differential effects on target cells.
Regular exercise training exerts pleiotropic cardio- and vascular-protective effects, including the reduction of systemic inflammation and improved vascular function via shear stress-mediated synthesis of nitric oxide and oxidative stress-induced upregulation of anti-oxidative mechanisms [8, 9]. In this setting, EV may serve as communication tools from leukocytes to endothelial cells.
This study assessed quantitative differences in circulating sEV and mEV and their differential impact on human endothelial cells when derived from patients with chronic coronary syndrome (CCS) or controls, as well as the potential of high-intensity exercise training (HIIT) to revert CCS-associated EV-mediated endothelial dysfunction and the quantitative composition of EV [10].
Patients with CCS exhibited higher plasma counts of leukocyte-derived mEV than age-matched healthy controls. In vitro re-endothelialisation capacity was promoted by mEV from controls, but not by mEV from CCS patients. HIIT for 4 weeks reduced plasma leukocyte-derived mEV in CCS patients and improved mEV-mediated support of in vitro re-endothelialisation. sEV from controls or CCS patients increased endothelial cell death and reduced repair functions and were not affected by HIIT.
Shear stress is accounted a major factor mediating the beneficial effect of regular exercise training on vascular health. In addition, metabolic factors might be linked to less systemic inflammatory activation. The present study adds the role of EV as mediators of inter-cellular and inter-organ communication in a dynamic systemic setting.
Future studies – besides addressing technical issues crucial for the validity and interpretation of findings [7] – may help better describing the role of individual types of EV in inter-organ interaction in the context of complex CV prevention measures and enable the development of monitoring strategies to fine-tune individual exercise protocols.
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