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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 hemodynamic 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 before, during, and throughout the recovery period after 1 h of moderate [46 \u00b1 2% maximal oxygen uptake (V\u0307o<jats:sub>2max<\/jats:sub>)] or heavy (67 \u00b1 2% V\u0307o<jats:sub>2max<\/jats:sub>) intensity semirecumbent 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<jats:sup>+<\/jats:sup>) increased from baseline only during heavy exercise (from 21 \u00b1 1 \u00d7 10<jats:sup>3<\/jats:sup>to 55 \u00b1 8 \u00d7 10<jats:sup>3<\/jats:sup>and 48 \u00b1 6 \u00d7 10<jats:sup>3<\/jats:sup>PMV\/\u03bcl at 30 and 60 min, respectively; P &lt; 0.05), returning to baseline early in postexercise recovery ( P &gt; 0.05), whereas EMVs (CD62E<jats:sup>+<\/jats:sup>) were unchanged ( P &gt; 0.05). PMVs were related to brachial artery shear rate ( r<jats:sup>2<\/jats:sup>= 0.43) and plasma norepinephrine concentrations ( r<jats:sup>2<\/jats:sup>= 0.21) during exercise ( P &lt; 0.05). Exercise-derived microvesicles enhanced endothelial proliferation, migration, and tubule formation compared with rest microvesicles ( P &lt; 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.<\/jats:p>","DOI":"10.1152\/ajpheart.00516.2016","type":"journal-article","created":{"date-parts":[[2016,9,17]],"date-time":"2016-09-17T02:49:33Z","timestamp":1474080573000},"page":"H1297-H1310","source":"Crossref","is-referenced-by-count":53,"title":["Exercise intensity modulates the appearance of circulating microvesicles with proangiogenic potential upon endothelial cells"],"prefix":"10.1152","volume":"311","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2679-0744","authenticated-orcid":false,"given":"Eurico N.","family":"Wilhelm","sequence":"first","affiliation":[{"name":"Centre for Human Performance, Exercise and Rehabilitation, College of Health and Life Sciences, Brunel University London, Uxbridge, United 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