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Browsing by Author "Gavin, Timothy P."
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Item Effects of home-based leg heat therapy on walking performance in patients with symptomatic peripheral artery disease: a pilot randomized trial(American Physiological Society, 2022) Monroe, Jacob C.; Pae, Byung Joon; Kargl, Christopher; Gavin, Timothy P.; Parker, Jason; Perkins, Susan M.; Han, Yan; Klein, Janet; Motaganahalli, Raghu L.; Roseguini, Bruno T.; Radiology and Imaging Sciences, School of MedicineFew noninvasive therapies currently exist to improve functional capacity in people with lower extremity peripheral artery disease (PAD). The goal of the present study was to test the hypothesis that unsupervised, home-based leg heat therapy (HT) using water-circulating trousers perfused with warm water would improve walking performance in patients with PAD. Patients with symptomatic PAD were randomized into either leg HT (n = 18) or a sham treatment (n = 16). Patients were provided with water-circulating trousers and a portable pump and were asked to apply the therapy daily (7 days/wk, 90 min/session) for 8 wk. The primary study outcome was the change from baseline in 6-min walk distance at 8-wk follow-up. Secondary outcomes included the claudication onset-time, peak walking time, peak pulmonary oxygen consumption and peak blood pressure during a graded treadmill test, resting blood pressure, the ankle-brachial index, postocclusive reactive hyperemia in the calf, cutaneous microvascular reactivity, and perceived quality of life. Of the 34 participants randomized, 29 completed the 8-wk follow-up. The change in 6-min walk distance at the 8-wk follow-up was significantly higher (P = 0.029) in the group exposed to HT than in the sham-treated group (Sham: median: -0.9; 25%, 75% percentiles: -5.8, 14.3; HT: median: 21.3; 25%, 75% percentiles: 10.1, 42.4, P = 0.029). There were no significant differences in secondary outcomes between the HT and sham group at 8-wk follow-up. The results of this pilot study indicate that unsupervised, home-based leg HT is safe, well-tolerated, and elicits a clinically meaningful improvement in walking tolerance in patients with symptomatic PAD. NEW & NOTEWORTHY: This is the first sham-controlled trial to examine the effects of home-based leg heat therapy (HT) on walking performance in patients with peripheral artery disease (PAD). We demonstrate that unsupervised HT using water-circulating trousers is safe, well-tolerated, and elicits meaningful changes in walking ability in patients with symptomatic PAD. This home-based treatment option is practical, painless, and may be a feasible adjunctive therapy to counteract the decline in lower extremity physical function in patients with PAD.Item Obesity and exercise training alter inflammatory pathway skeletal muscle small extracellular vesicle microRNAs(Wiley, 2022) Sullivan, Brian P.; Nie, Yaohui; Evans, Sheelagh; Kargl, Chris K.; Hettinger, Zach R.; Garner, Ron T.; Hubal, Monica J.; Kuang, Shihuan; Stout, Julianne; Gavin, Timothy P.; Kinesiology, School of Health and Human SciencesObesity is associated with chronic inflammation characterized by increased levels of inflammatory cytokines, whereas exercise training reduces inflammation. Small extracellular vesicles (EVs; 30–150 nm) participate in cell‐to‐cell communication in part through microRNA (miRNA) post‐transcriptional regulation of mRNA. We examined whether obesity and concurrent aerobic and resistance exercise training alter skeletal muscle EV miRNA content and inflammatory signalling. Vastus lateralis biopsies were obtained from sedentary individuals with (OB) and without obesity (LN). Before and after 7 days of concurrent aerobic and resistance training, muscle‐derived small EV miRNAs and whole‐muscle mRNAs were measured. Pathway analysis revealed that obesity alters small EV miRNAs that target inflammatory (SERPINF1, death receptor and Gαi) and growth pathways (Wnt/β‐catenin, PTEN, PI3K/AKT and IGF‐1). In addition, exercise training alters small EV miRNAs in an anti‐inflammatory manner, targeting the IL‐10, IL‐8, Toll‐like receptor and nuclear factor‐κB signalling pathways. In whole muscle, IL‐8 mRNA was reduced by 50% and Jun mRNA by 25% after exercise training, consistent with the anti‐inflammatory effects of exercise on skeletal muscle. Obesity and 7 days of concurrent exercise training differentially alter skeletal muscle‐derived small EV miRNA contents targeting inflammatory and anabolic pathways.Item Peroxisome proliferator-activated receptor γ coactivator 1-α overexpression improves angiogenic signalling potential of skeletal muscle-derived extracellular vesicles(Wiley, 2023) Kargl, Chris K.; Sullivan, Brian P.; Middleton, Derek; York, Andrew; Burton, Lundon C.; Brault, Jeffrey J.; Kuang, Shihuan; Gavin, Timothy P.; Anatomy, Cell Biology and Physiology, School of MedicineNew findings: What is the central question of this study? Skeletal muscle extracellular vesicles likely act as pro-angiogenic signalling factors: does overexpression of peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) alter skeletal muscle myotube extracellular vesicle release, contents and angiogenic potential? What is the main finding and its importance? Overexpression of PGC-1α results in secretion of extracellular vesicles that elevate measures of angiogenesis and protect against acute oxidative stress in vitro. Skeletal muscle with high levels of PGC-1α expression, commonly associated with exercise induced angiogenesis and high basal capillarization, may secrete extracellular vesicles that support capillary growth and maintenance. Abstract: Skeletal muscle capillarization is proportional to muscle fibre mitochondrial content and oxidative capacity. Skeletal muscle cells secrete many factors that regulate neighbouring capillary endothelial cells (ECs), including extracellular vesicles (SkM-EVs). Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) regulates mitochondrial biogenesis and the oxidative phenotype in skeletal muscle. Skeletal muscle PGC-1α also regulates secretion of multiple angiogenic factors, but it is unknown whether PGC-1α regulates SkM-EV release, contents and angiogenic signalling potential. PGC-1α was overexpressed via adenovirus in primary human myotubes. EVs were collected from PGC-1α-overexpressing myotubes (PGC-EVs) as well as from green fluorescent protein-overexpressing myotubes (GFP-EVs), and from untreated myotubes. EV release and select mRNA contents were measured from EVs. Additionally, ECs were treated with EVs to measure angiogenic potential of EVs in normal conditions and following an oxidative stress challenge. PGC-1α overexpression did not impact EV release but did elevate EV content of mRNAs for several antioxidant proteins (nuclear factor erythroid 2-related factor 2, superoxide dismutase 2, glutathione peroxidase). PGC-EV treatment of cultured human umbilical vein endothelial cells (HUVECs) increased their proliferation (+36.6%), tube formation (length: +28.1%; number: +25.7%) and cellular viability (+52.9%), and reduced reactive oxygen species levels (-41%) compared to GFP-EVs. Additionally, PGC-EV treatment protected against tube formation impairments and induction of cellular senescence following acute oxidative stress. Overexpression of PGC-1α in human myotubes increases the angiogenic potential of SkM-EVs. These angiogenic benefits coincided with increased anti-oxidative capacity of recipient HUVECs. High PGC-1α expression in skeletal muscle may prompt the release of SkM-EVs that support vascular redox homeostasis and angiogenesis.