Sedentariness, environmental conditions and vascular remodelling

Marc Antoine Custaud, PU-PH

macustaud@chu-angers.fr (macustaud @ chu-angers.fr)

M.A. Custaud PU-PH,

P.M. Roy PU-PH,

J.O. Fortrat MCU-PH,

N. Navasiolava PhD.

Sedentariness is among the most important behavioral risk factors for cardiovascular disease. Because fighting gravity requires daily physical efforts, exposure to microgravity is associated with enhanced physical inactivity . Microgravity and its long-term simulations– bed rest, head-down bed rest (HDBR), and dry immersion—offer unique models for studying the effects of global physical inactivity in healthy individuals.
Inactivity, with decrease in resting blood blow and chronic decrease in shear stress, is associated with remodeling of conduit arteries and functional impairment of small vessels at lower limb level. Conduit arteries undergo structural (decrease in diameter, increase in IMT, decrease in compliance) and functional (no change or decrease in endothelial (FMD) and smooth muscle (nitroglycerin reactivity) changes, whereas resistive arteries undergo increase in vascular resistance and endothelial impairment. Venous properties at the leg level are also changed, with compliance increases and venous emptying capacities are impaired.
Vascular changes are closely linked to a syndrome of cardiovascular deconditioning to gravity and to physical exercise and are associated to an increase of the vascular risk.

Our aim is to

• Continue to study the mechanisms of endothelial dysfunction in humans induced by sedentariness with a specific emphasis on circulating factors and on the link between endothelial functions, platelet functions and leucocyte functions.
• Develop new tools in order to study venous functions
• Perform integrative studies of vascular functions (arterial side, microcirculation side, venous side and arterio-venous reflex) at the leg level in humans subject to enhanced physical inactivity.
• Test new countermeasures and combination of countermeasures based on artificial gravity and physical exercise to prevent cardiovascular deconditioning
• Promote the use of the dry immersion program for research (as model of enhanced physical inactivity and of weightlessness) and therapeutics.

International collaborations

• Dublin City University, Ireland
• IBMP : Institute of biomedical problems, Moscow, Russia
• ACC : Chinese astronautic center, Beijing, China

Main publications

• Navasiolava NM, Dignat-George F, Sabatier F, Larina IM, Demiot C, Fortrat JO, Gauquelin-Koch G, Kozlovskaya IB, Custaud MA. Enforced physical inactivity increases endothelial microparticle levels in healthy volunteers. Am J Physiol Heart Circ Physiol. 2010 Aug;299(2):H248-56.
• Navasiolava NM, Custaud MA, Tomilovskaya ES, Larina IM, Mano T, Gauquelin- Koch G, Gharib C, Kozlovskaya IB. Long-term dry immersion: review and prospects. Eur J Appl Physiol. 2011 Jul;111(7):1235-60.
• Amirova LE, Navasiolava NM, Bareille MP, Beck A, Tomilovskaya ES, Kozlovzkaya IB, Gauquelin-Koch G, Gharib C, Custaud MA. Effects of plantar stimulation on cardiovascular response to orthostatism. Eur J Appl Physiol. 2016 Dec;116(11-12):2257-2266.
• De Abreu S, Amirova L, Murphy R, Wallace R, Twomey L, Gauquelin-Koch G, Raverot V, Larcher F, Custaud MA, Navasiolava N. Multi-System Deconditioning in 3-Day Dry Immersion without Daily Raise. Front Physiol. 2017 Oct 13;8:799.
• Wallace RG, Twomey LC, Custaud MA, Turner JD, Moyna N, Cummins PM, Murphy RP. The role of epigenetics in cardiovascular health and ageing: A focus on physical activity and nutrition. Mech Ageing Dev. 2018 Sep;174:76-85.
• Yuan M, Custaud MA, Xu Z, Wang J, Yuan M, Tafforin C, Treffel L, Arbeille P, Nicolas M, Gharib C, Gauquelin-Koch G, Arnaud L, Lloret JC, Li Y, Navasiolava N. Multi-System Adaptation to Confinement During the 180-Day Controlled Ecological Life Support System (CELSS) Experiment. Front Physiol. 2019 May 21;10:575.
• Navasiolava N, Yuan M, Murphy R, Robin A, Coupé M, Wang L, Alameddine A, Gauquelin-Koch G, Gharib C, Li Y, Custaud MA. Vascular and Microvascular Dysfunction Induced by Microgravity and Its Analogs in Humans: Mechanisms and Countermeasures. Front Physiol. 2020 Aug 20;11:952.