title: Increased local cytokine production at culprit superficial femoral artery plaques.
abstract: Characterization of local inflammation at culprit superficial femoral artery (SFA) stenosis has not been studied. We hypothesized that arterial cytokine concentrations would be greater at sites of stenosis. Twenty patients with ≥50 % angiographic stenosis of the SFA had blood drawn just proximal to the lesion and from a contralateral site free of disease. A microplate immunoassay was used to determine the concentrations of 42 distinct cytokines and growth factors. Exact conditional logistic analysis was used to compare measures at the two sites with interaction terms describing clinical factors used to identify difference mediators. Interaction terms identified clinical factors that could predict cytokine levels. The concentrations of soluble CD40 ligand (sCD40L; mean 212 and 177 pg/ml, p = 0.01) and tumor necrosis factor beta (TNF-B; mean 16.6 and 15.9 pg/ml, p = 0.04) were increased immediately proximal to areas of stenosis. Factors associated with greater concentrations at sites of stenosis were bilateral ankle-brachial index ≤0.90 (p = 0.04), no statin use (p = 0.02), claudication (p = 0.03), low leukocyte count (p = 0.03), absence of limb ischemia (p = 0.04) and lack of aspirin or clopidogrel therapy (p ≤ 0.06). Greater concentrations of sCD40L and TNF-B at sites of stenosis suggest that these cytokines play a role in the pathogenesis of symptomatic SFA disease. Our results also suggest that statin, aspirin and clopidogrel therapy may attenuate localized inflammation in the SFA, though due to a small sample size and the use of multiple comparisons across groups, these findings can be viewed as hypothesis generating only. In conclusion, selected cytokines are heightened at culprit SFA lesions and inflammation may be modulated by statin and antiplatelet therapy.
authors.affiliation: College of Medicine, University of Vermont, Burlington, VT, USA, cameron.donaldson@vtmednet.org.
authors.forename: Cameron W
authors.initials: CW
authors.lastname: Donaldson
authors.forename: David J
authors.initials: DJ
authors.lastname: Schneider
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Bertges
authors.forename: Julie E
authors.initials: JE
authors.lastname: Adams
authors.forename: Nader Z
authors.initials: NZ
authors.lastname: Elgharib
authors.forename: Enkhtuyaa L
authors.initials: EL
authors.lastname: Mueller
authors.forename: William
authors.initials: W
authors.lastname: Prabhu
authors.forename: Taka
authors.initials: T
authors.lastname: Ashikaga
authors.forename: Harold L
authors.initials: HL
authors.lastname: Dauerman
mesh_terms: D001241:Aspirin / Q000008:administration & dosage; D023201:CD40 Ligand / Q000097:blood*; D000077144:Clopidogrel; D003251:Constriction, Pathologic / Q000097:blood / Q000188:drug therapy; D005260:Female; D005263:Femoral Artery; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D007511:Ischemia / Q000097:blood / Q000188:drug therapy; D035002:Lower Extremity / Q000098:blood supply; D008233:Lymphotoxin-alpha / Q000097:blood*; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000188:drug therapy; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011446:Prospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008233:Lymphotoxin-alpha; D010975:Platelet Aggregation Inhibitors; D023201:CD40 Ligand; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin