title: Exercise training in intermittent claudication: effects on antioxidant genes, inflammatory mediators and proangiogenic progenitor cells.
abstract: Exercise training remains a therapy of choice in intermittent claudication (IC). However, too exhaustive exercise may cause ischaemic injury and inflammatory response. We tested the impact of three-month treadmill training and single treadmill exercise on antioxidant gene expressions, cytokine concentrations and number of marrow-derived proangiogenic progenitor cells (PPC) in the blood of IC patients. Blood samples of 12 patients were collected before and after training, before and 1, 3 and 6 hours after the single exercise. PPCs were analysed with flow cytometry, cytokine concentrations were checked with Milliplex MAP, while expression of mRNAs and miRNAs was evaluated with qRT-PCR. Treadmill training improved pain-free walking time (from 144 ± 44 seconds [s] to 311 ± 134 s, p=0.02) and maximum walking time (from 578 ± 293 s to 859 ± 423 s, p=0.01) in IC patients. Before, but not after training, the single treadmill exercise increased the number of circulating CD45dimCD34+CD133-KDR+ PPCs (p=0.048), decreased expression of  HMOX1  (p=0.04) in circulating leukocytes, reduced tumour necrosis factor-α (p=0.03) and tended to elevate myeloperoxidase (p=0.06) concentrations in plasma. In contrast, total plasminogen activator inhibitor-1 was decreased by single exercise only after, but not before training (p=0.02). Both before and after training the single exercise decreased monocyte chemoattractant protein (MCP)-1 (p=0.006 and p=0.03) concentration and increased  SOD1  (p=0.001 and p=0.01) expression. Patients after training had also less interleukin-6 (p=0.03), but more MCP-1 (p=0.04) in the blood. In conclusion, treadmill training improves walking performance of IC patients, attenuates the single exercise-induced changes in gene expressions or PPC mobilisation, but may also lead to higher production of some proinflammatory cytokines.
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Witold N
authors.initials: WN
authors.lastname: Nowak
authors.forename: Piotr
authors.initials: P
authors.lastname: Mika
authors.forename: Roman
authors.initials: R
authors.lastname: Nowobilski
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kusinska
authors.forename: Karolina
authors.initials: K
authors.lastname: Bukowska-Strakova
authors.forename: Rafal
authors.initials: R
authors.lastname: Nizankowski
authors.forename: Alicja
authors.initials: A
authors.lastname: Józkowicz
authors.forename: Andrzej
authors.initials: A
authors.lastname: Szczeklik
authors.forename: Jozef
authors.initials: J
authors.lastname: Dulak
mesh_terms: D053687:Adult Stem Cells / Q000473:pathology; D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D001157:Arterial Occlusive Diseases / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D018932:Chemokine CCL2 / Q000097:blood; D016207:Cytokines / Q000097:blood; D005081:Exercise Therapy; D005260:Female; D015870:Gene Expression; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007383:Intermittent Claudication / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D058729:Peripheral Arterial Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D016138:Walking / Q000502:physiology
chemical_list: D000975:Antioxidants; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D012333:RNA, Messenger; C000606290:SOD1 protein, human; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1