Exercise intensity modulates the appearance of circulating microvesicles with pro-angiogenic potential upon endothelial cells.

Abstract

The effect of endurance exercise on circulating microvesicle dynamics and their impact upon surrounding endothelial cells is unclear. Here we tested the hypothesis that exercise intensity modulates the time-course of platelet (PMV) and endothelial-derived (EMV) microvesicle appearance in the circulation through haemodynamic and biochemical-related mechanisms, and that microvesicles formed during exercise would stimulate endothelial angiogenesis in vitro. Nine healthy young men had venous blood samples taken prior, during and throughout the recovery period after 1 h of moderate (46±2% V̇O2max) or heavy (67±2% V̇O2max) intensity semi-recumbent cycling and a time matched resting control trial. In vitro experiments were performed by incubating endothelial cells with rest and exercise-derived microvesicles to examine their effects on cell angiogenic capacities. PMVs (CD41+) increased from baseline only during heavy exercise (from 21±1 x 103 to 55±8 x 103 and 48±6 x 103 PMV / μl at 30 and 60 min, respectively; P < 0.05), returning to baseline early in post-exercise recovery (P > 0.05), whereas EMVs (CD62E+) were unchanged (P > 0.05). PMVs were related to brachial artery shear rate (r2 = 0.43) and plasma noradrenaline concentrations (r2 = 0.21) during exercise (P < 0.05). Exercise-derived microvesicles enhanced endothelial proliferation, migration and tubule formation compared to rest microvesicles (P < 0.05). These results demonstrate substantial increases in circulating PMVs during heavy exercise and that exercise-derived microvesicles stimulate human endothelial cells by enhancing angiogenesis and proliferation. This involvement of microvesicles may be considered a novel mechanism through which exercise mediates vascular healing and adaptation.