title: Exercise intensity modulates the appearance of circulating microvesicles with proangiogenic potential upon endothelial cells.
abstract: The effect of endurance exercise on circulating microvesicle dynamics and their impact on 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 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 ± 2% maximal oxygen uptake (V̇o2max)] or heavy (67 ± 2% V̇o2max) 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+) increased from baseline only during heavy exercise (from 21 ± 1 × 103to 55 ± 8 × 103and 48 ± 6 × 103PMV/μl at 30 and 60 min, respectively; P < 0.05), returning to baseline early in postexercise 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 norepinephrine concentrations (r2= 0.21) during exercise (P < 0.05). Exercise-derived microvesicles enhanced endothelial proliferation, migration, and tubule formation compared with 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.
authors.affiliation: Centre for Human Performance, Exercise and Rehabilitation, College of Health and Life Sciences, Brunel University London, Uxbridge, United Kingdom.
authors.forename: Eurico N
authors.identifier: 0000-0003-2679-0744
authors.initials: EN
authors.lastname: Wilhelm
authors.affiliation: Centre for Human Performance, Exercise and Rehabilitation, College of Health and Life Sciences, Brunel University London, Uxbridge, United Kingdom.
authors.forename: José
authors.initials: J
authors.lastname: González-Alonso
authors.affiliation: Institute for the Environment, Health and Societies, Brunel University London, Uxbridge, United Kingdom; and.
authors.forename: Christopher
authors.initials: C
authors.lastname: Parris
authors.affiliation: Faculty of Science, Department of Biological Sciences, Thompson Rivers University Kamloops, British Columbia, Canada mrakobowchuk@tru.ca.
authors.forename: Mark
authors.identifier: 0000-0002-1965-3277
authors.initials: M
authors.lastname: Rakobowchuk
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000502:physiology*; D001916:Brachial Artery; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D055252:Cell-Derived Microparticles / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology*; D015444:Exercise / Q000502:physiology*; D064368:Healthy Volunteers; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption; D010807:Physical Endurance; D012146:Rest / Q000502:physiology; D055815:Young Adult
chemical_list: D009638:Norepinephrine
keywords: angiogenesis; human umbilical vein endothelial cell; microparticles; platelet microvesicles; shear stress