title: Resistive Training and Molecular Regulators of Vascular-Metabolic Risk in Chronic Stroke.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC-1α) gene and Sirtuin-1 (SIRT-1) respond to physiological stimuli and regulate insulin resistance. Inflammatory markers tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), and the soluble forms of intracellular adhesion molecule (sICAM-1) and vascular CAM-1 (sVCAM-1) are associated with increased risk of diabetes and coronary heart disease. Resistive training (RT) reduces hyperinsulinemia and improves insulin action in chronic stroke. Yet, the molecular mechanisms for this are unknown. This study will determine the effects of RT on skeletal muscle PGC-1α and SIRT-1 mRNA expression and inflammatory and vascular markers.
  
  
  METHODS
  Stroke survivors (50-76 years) underwent a fasting blood draw for measurement of TNF-α, IL-6, CRP, serum amyloid A, sICAM-1, sVCAM-1, and bilateral vastus lateralis biopsies before and after RT. Participants were also assessed using bilateral multislice thigh computed tomography scans from the knee to the hip, a total body scan by dual-energy X-ray absorptiometry, and 1-repetition maximum strength testing. Subjects performed 2 sets of 3 lower extremity RT exercises 3 times per week for 12 weeks.
  
  
  RESULTS
  Bilateral leg press and leg extension strength increased ~30-50% with RT (P < .001). Body weight, total body fat mass, and fat-free mass did not change. Thigh muscle area and volume increased in both legs (P < .05). Nonparetic muscle PGC-1α mRNA expression increased 14% (P < .05) after RT and SIRT-1 mRNA decreased 24% (P < .05) and 31% (P < .01) in paretic and nonparetic muscles. There were no significant changes in plasma inflammation with training.
  
  
  CONCLUSIONS
  RT in chronic stroke induces changes in key skeletal muscle regulators of metabolism, without effecting circulating inflammation.
authors.affiliation: Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland; GRECC, MERCE, Baltimore, Maryland. Electronic address: aryan@grecc.umaryland.edu.
authors.forename: Alice S
authors.initials: AS
authors.lastname: Ryan
authors.affiliation: Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland; GRECC, MERCE, Baltimore, Maryland.
authors.forename: Guoyan
authors.initials: G
authors.lastname: Li
authors.affiliation: GRECC, MERCE, Baltimore, Maryland; Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Charlene
authors.initials: C
authors.lastname: Hafer-Macko
authors.affiliation: GRECC, MERCE, Baltimore, Maryland; Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Ivey
mesh_terms: D015502:Absorptiometry, Photon; D050154:Adiposity; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D018836:Inflammation Mediators / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D061330:Multidetector Computed Tomography; D009119:Muscle Contraction; D053580:Muscle Strength; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism; D052097:Quadriceps Muscle / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055070:Resistance Training; D012307:Risk Factors; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D020521:Stroke / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D000071939:Stroke Rehabilitation / Q000379:methods*; D016896:Treatment Outcome; D051598:Whole Body Imaging
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D016207:Cytokines; D018836:Inflammation Mediators; D007328:Insulin; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Exercise; inflammation; skeletal muscle; strength; stroke; vascular