title: Alteration in angiogenic and anti-angiogenic forms of vascular endothelial growth factor-A in skeletal muscle of patients with intermittent claudication following exercise training.
abstract: The aims of this study were twofold: (1) to identify whether peripheral artery disease (PAD) patients had increased muscle concentration of angiogenic VEGF-A, anti-angiogenic VEGF₁₆₅b or VEGF receptor 1 (VEGF-R1) when compared with control subjects, and (2) to evaluate whether exercise training in PAD patients was associated with changes in muscle concentration of VEGF-A, VEGF₁₆₅b or VEGF-R1. At baseline, 22 PAD and 30 control subjects underwent gastrocnemius muscle biopsy. Twelve PAD patients were treated with supervised exercise training (SET) and underwent muscle biopsy after 3 weeks and 12 weeks of training and had sufficient tissue to measure VEGF-A, VEGF₁₆₅b and VEGF-R1 concentrations in skeletal muscle lysates by ELISA. Muscle concentrations of VEGF-A and VEGF₁₆₅b were similar in PAD patients versus controls at baseline. At both time points after the start of SET, VEGF-A levels decreased and there was a trend towards increased VEGF₁₆₅b concentrations. At baseline, VEGF-R1 concentrations were lower in PAD patients when compared with controls but did not change after SET. Skeletal muscle concentrations of VEGF-A are not different in PAD patients when compared with controls at baseline. SET is associated with a significant reduction in VEGF-A levels and a trend towards increased VEGF₁₆₅b levels. These somewhat unexpected findings suggest that further investigation into the mechanism of vascular responses to exercise training in PAD patients is warranted.
authors.affiliation: Division of Cardiology, Duke University Medical Center, Durham, NC, USA. schuyler.jones@duke.edu
authors.forename: W Schuyler
authors.initials: WS
authors.lastname: Jones
authors.forename: Brian D
authors.initials: BD
authors.lastname: Duscha
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Robbins
authors.forename: Natasha N
authors.initials: NN
authors.lastname: Duggan
authors.forename: Judith G
authors.initials: JG
authors.lastname: Regensteiner
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.forename: William R
authors.initials: WR
authors.lastname: Hiatt
authors.forename: Ayotunde O
authors.initials: AO
authors.lastname: Dokun
authors.forename: Brian H
authors.initials: BH
authors.lastname: Annex
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D001706:Biopsy; D002196:Capillaries / Q000503:physiopathology; D003120:Colorado; D004797:Enzyme-Linked Immunosorbent Assay; D005081:Exercise Therapy; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D007383:Intermittent Claudication / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D009657:North Carolina; D058729:Peripheral Arterial Disease / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D020127:Recovery of Function; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1