title: Enforced physical inactivity increases endothelial microparticle levels in healthy volunteers.
abstract: A sedentary lifestyle has adverse effects on the cardiovascular system, including impaired endothelial functions. Subjecting healthy men to 7 days of dry immersion (DI) presented a unique opportunity to analyze the specific effects of enhanced inactivity on the endothelium. We investigated endothelial properties before, during, and after 7 days of DI involving eight subjects. Microcirculatory functions were assessed with laser Doppler in the skin of the calf. We studied basal blood flow and endothelium-dependent and -independent vasodilation. We also measured plasma levels of microparticles, a sign of cellular dysfunction, and soluble endothelial factors, reflecting the endothelial state. Basal flow and endothelium-dependent vasodilation were reduced by DI (22 + or - 4 vs. 15 + or - 2 arbitrary units and 29 + or - 6% vs. 12 + or - 6%, respectively, P < 0.05), and this was accompanied by an increase in circulating endothelial microparticles (EMPs), which was significant on day 3 (42 + or - 8 vs. 65 + or - 10 EMPs/microl, P < 0.05), whereas microparticles from other cell origins remained unchanged. Plasma soluble VEGF decreased significantly during DI, whereas VEGF receptor 1 and soluble CD62E were unchanged, indicating that the increase in EMPs was associated with a change in antiapoptotic tone rather than endothelial activation. Our study showed that extreme physical inactivity in humans induced by 7 days of DI causes microvascular impairment with a disturbance of endothelial functions, associated with a selective increase in EMPs. Microcirculatory endothelial dysfunction might contribute to cardiovascular deconditioning as well as to hypodynamia-associated pathologies. In conclusion, the endothelium should be the focus of special care in situations of acute limitation of physical activity.
authors.affiliation: Centre National de la Recherche Scientifique UMR 6214, Institut National de la Santé et de la Recherche Médicale U771, Faculté de Médecine, Angers 49045, France.
authors.forename: Nastassia M
authors.initials: NM
authors.lastname: Navasiolava
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
authors.forename: Florence
authors.initials: F
authors.lastname: Sabatier
authors.forename: Irina M
authors.initials: IM
authors.lastname: Larina
authors.forename: Claire
authors.initials: C
authors.lastname: Demiot
authors.forename: Jacques-Olivier
authors.initials: JO
authors.lastname: Fortrat
authors.forename: Guillemette
authors.initials: G
authors.lastname: Gauquelin-Koch
authors.forename: Inesa B
authors.initials: IB
authors.lastname: Kozlovskaya
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Custaud
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage; D000279:Administration, Cutaneous; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000473:pathology*; D019040:E-Selectin / Q000097:blood; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007478:Iontophoresis; D017078:Laser-Doppler Flowmetry; D007866:Leg; D008055:Lipids / Q000097:blood; D008297:Male; D008833:Microcirculation; D009599:Nitroprusside / Q000008:administration & dosage; D057185:Sedentary Behavior; D012867:Skin / Q000098:blood supply*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood; D014664:Vasodilation; D014665:Vasodilator Agents / Q000008:administration & dosage; D018474:Weightlessness Simulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D019040:E-Selectin; D008055:Lipids; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014665:Vasodilator Agents; D009599:Nitroprusside; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D000109:Acetylcholine