title: Effects of normoxic and hypoxic exercise regimens on monocyte-mediated thrombin generation in sedentary men.
abstract: Exercise and hypoxia paradoxically modulate vascular thrombotic risks. The shedding of procoagulant-rich microparticles from monocytes may accelerate the pathogenesis of atherothrombosis. The present study explores the manner in which normoxic and hypoxic exercise regimens affect procoagulant monocyte-derived microparticle (MDMP) formation and monocyte-promoted thrombin generation (TG). Forty sedentary healthy males were randomized to perform either normoxic (NET; 21% O2, n=20) or hypoxic (HET; 15% O2, n=20) exercise training (60% VO(2max)) for 30 min/day, 5 days/week for 5 weeks. At rest and immediately after HET (100 W under 12% O2 for 30 min), the MDMP characteristics and dynamic TG were measured by flow cytometry and thrombinography respectively. The results demonstrated that acute 12% O2 exercise (i) increased the release of coagulant factor V (FV)/FVIII-rich, phosphatidylserine (PS)-exposed and tissue factor (TF)-expressed microparticles from monocytes, (ii) enhanced the peak height and rate of TG in monocyte-rich plasma (MRP) and (iii) elevated concentrations of norepinephrine/epinephrine, myeloperoxidase (MPO) and interleukin-6 (IL-6) in plasma. Following the 5-week intervention, HET exhibited higher enhancements of peak work-rate and cardiopulmonary fitness than NET did. Moreover, both NET and HET decreased the FV/FVIII-rich, PS-exposed and TF-expressed MDMP counts and the peak height and rate of TG in MRP following the HET. However, HET elicited more suppression for the HE (hypoxic exercise)-enhanced procoagulant MDMP formation and dynamic TG in MPR and catecholamine/peroxide/pro-inflammatory cytokine levels in plasma than NET. Hence, we conclude that HET is superior to NET for enhancing aerobic capacity. Furthermore, HET effectively suppresses procoagulant MDMP formation and monocyte-mediated TG under severe hypoxic stress, compared with NET.
authors.affiliation: *Healthy Aging Research Center, Graduate Institute of Rehabilitation Science, Medical Collage, Chang Gung University, Tao-Yuan 333, Taiwan.
authors.forename: Jong-Shyan
authors.initials: JS
authors.lastname: Wang
authors.affiliation: *Healthy Aging Research Center, Graduate Institute of Rehabilitation Science, Medical Collage, Chang Gung University, Tao-Yuan 333, Taiwan.
authors.forename: Ya-Lun
authors.initials: YL
authors.lastname: Chang
authors.affiliation: *Healthy Aging Research Center, Graduate Institute of Rehabilitation Science, Medical Collage, Chang Gung University, Tao-Yuan 333, Taiwan.
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Chen
authors.affiliation: *Healthy Aging Research Center, Graduate Institute of Rehabilitation Science, Medical Collage, Chang Gung University, Tao-Yuan 333, Taiwan.
authors.forename: Hsing-Hua
authors.initials: HH
authors.lastname: Tsai
authors.affiliation: †Heart Failure Center, Chang Gung Memorial Hospital, Keelung 204, Taiwan.
authors.forename: Tieh-Cheng
authors.initials: TC
authors.lastname: Fu
mesh_terms: D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D002395:Catecholamines / Q000097:blood; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D016207:Cytokines / Q000097:blood; D015444:Exercise; D005165:Factor V / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000097:blood* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D009195:Peroxidase / Q000097:blood; D010809:Physical Fitness; D057185:Sedentary Behavior; D013624:Taiwan; D013917:Thrombin / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D002395:Catecholamines; D016207:Cytokines; D018836:Inflammation Mediators; C078147:F8 protein, human; D005165:Factor V; D005169:Factor VIII; D009195:Peroxidase; D013917:Thrombin