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Abstract
Ground based research modalities of microgravity have been proposed as innovative methods to investigate the aetiology of chronic age-related conditions such as cardiovascular disease. Dry Immersion (DI), has been effectively used to interrogate the sequelae of physical inactivity (PI) and microgravity on multiple physiological systems. Herein we look at the causa et effectus of 3-day DI on platelet phenotype, and correlate with both miRomic and circulating biomarker expression. The miRomic profile of platelets is reflective of phenotype, which itself is sensitive and malleable to the exposome, undergoing responsive transitions in order to fulfil platelets role in thrombosis and haemostasis. Heterogeneous platelet subpopulations circulate at any given time, with varying degrees of sensitivity to activation. Employing a DI model, we investigate the effect of acute PI on platelet function in 12 healthy males. 3-day DI resulted in a significant increase in platelet count, plateletcrit, platelet adhesion, aggregation, and a modest elevation of platelet reactivity index (PRI). We identified 15 protein biomarkers and 22 miRNA whose expression levels were altered after DI. A 3-day DI model of microgravity/physical inactivity induced a prothrombotic platelet phenotype with an unique platelet miRNA signature, increased platelet count and plateletcrit. This correlated with a unique circulating protein biomarker signature. Taken together, these findings highlight platelets as sensitive adaptive sentinels and functional biomarkers of epigenetic drift within the cardiovascular compartment.
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1 Technological University Dublin, Dublin 9, Ireland (GRID:grid.497880.a); Dublin City University, Cell & Molecular Physiology Group, School of Health & Human Performance, Faculty of Science and Health, Dublin 9, Ireland (GRID:grid.15596.3e) (ISNI:0000000102380260)
2 Univ Angers, CHU Angers, CRC, Inserm, CNRS, MITOVASC, SFR ICAT, Angers, France (GRID:grid.411147.6) (ISNI:0000 0004 0472 0283)
3 MEDES, Toulouse, France (GRID:grid.435966.b)
4 Centre National d’Études Spatiales (CNES), Paris, France (GRID:grid.13349.3c) (ISNI:0000 0001 2201 6490)
5 Univ Angers, CHU Angers, Laboratoire de Biochimie, Angers, France (GRID:grid.7252.2) (ISNI:0000 0001 2248 3363)
6 University College Cork, Department of Pharmacology and Therapeutics, Cork, Ireland (GRID:grid.7872.a) (ISNI:0000000123318773)
7 The Chinese University of Hong Kong, Department of Sports Science & Physical Education, Hong Kong, China (GRID:grid.10784.3a) (ISNI:0000 0004 1937 0482)
8 University College Dublin, Conway-SPHERE Research Group, Conway Institute, Dublin, Ireland (GRID:grid.7886.1) (ISNI:0000 0001 0768 2743)
9 Waterford Institute of Technology, Department of Sport and Exercise Science, Waterford, Ireland (GRID:grid.24349.38) (ISNI:0000000106807997)
10 Dublin City University, Cell & Molecular Physiology Group, School of Health & Human Performance, Faculty of Science and Health, Dublin 9, Ireland (GRID:grid.15596.3e) (ISNI:0000000102380260); DCU, Centre for Preventive Medicine, Glasnevin, Ireland (GRID:grid.15596.3e) (ISNI:0000000102380260)
11 School of Health & Human Performance, DCU, Vascular Physiology and Clinical Exercise Medicine Group, Glasnevin, Ireland (GRID:grid.15596.3e) (ISNI:0000000102380260); DCU, Centre for Preventive Medicine, Glasnevin, Ireland (GRID:grid.15596.3e) (ISNI:0000000102380260)
12 Université de Lyon, Institut NeuroMyoGène, Faculté de Médecine Lyon-Est, Lyon, France (GRID:grid.25697.3f) (ISNI:0000 0001 2172 4233)