title: Association of monocyte tumor necrosis factor α expression and serum inflammatory biomarkers with walking impairment in peripheral artery disease.
abstract: OBJECTIVE
  Inflammation contributes to the development of peripheral artery disease (PAD) and may contribute to intermittent claudication by adversely affecting vascular and skeletal muscle function. We explored the association of inflammation to maximal walking time (MWT) in patients with claudication.
  
  
  METHODS
  Circulating inflammatory biomarkers, including tumor necrosis factor α (TNF-α), C-reactive protein (CRP), interleukin-6 (IL-6), and soluble intercellular adhesion molecule 1 (sICAM), were measured in 75 subjects with intermittent claudication as well as in 43 healthy subjects. Real-time polymerase chain reaction was used to quantify mRNA expression of TNF-α, IL-6, interferon-γ, and CD36 from peripheral blood monocytes. Treadmill testing was performed in PAD subjects to assess MWT.
  
  
  RESULTS
  Compared with healthy subjects, PAD subjects had higher levels of circulating TNF-α (P < .0001), CRP (P = .003), sICAM (P < .0001), and IL-6 (P < .0001). Expression of both IL-6 (P = .024) and CD36 (P = .018) was greater in PAD subjects than in healthy subjects. Among subjects with PAD, higher gene expression of TNF-α was associated inversely with MWT (P = .01). MWT was also associated inversely with greater levels of circulating TNF-α (P = .028), CRP (P = .024), IL-6 (P = .03), and sICAM (P = .018).
  
  
  CONCLUSIONS
  Systemic inflammation, as indicated by TNF-α inflammatory gene expression in peripheral blood monocytes and by circulating biomarker levels, is associated with impairment in walking time in patients with PAD and intermittent claudication.
authors.affiliation: Cardiovascular Division, Vascular Medicine Section, Brigham and Women's Hospital, Boston, Mass. Electronic address: rpande@partners.org.
authors.forename: Reena L
authors.initials: RL
authors.lastname: Pande
authors.affiliation: Cardiovascular Division, Vascular Medicine Section, Brigham and Women's Hospital, Boston, Mass.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Brown
authors.affiliation: Cardiovascular Division, Vascular Medicine Section, Brigham and Women's Hospital, Boston, Mass.
authors.forename: Stewart
authors.initials: S
authors.lastname: Buck
authors.affiliation: Cardiovascular Division, Vascular Medicine Section, Brigham and Women's Hospital, Boston, Mass.
authors.forename: Whitney
authors.initials: W
authors.lastname: Redline
authors.affiliation: Cardiovascular Division, Vascular Medicine Section, Brigham and Women's Hospital, Boston, Mass.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Doyle
authors.affiliation: Cardiovascular Division, Vascular Medicine Section, Brigham and Women's Hospital, Boston, Mass.
authors.forename: Jorge
authors.initials: J
authors.lastname: Plutzky
authors.affiliation: Cardiovascular Division, Vascular Medicine Section, Brigham and Women's Hospital, Boston, Mass.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Creager
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005080:Exercise Test; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007383:Intermittent Claudication / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D058729:Peripheral Arterial Disease / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000097:blood; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000235:genetics; D016138:Walking
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha
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