title: Circulating inflammatory cells are associated with vein graft stenosis.
abstract: OBJECTIVE
  Infrainguinal autogenous vein grafts are especially prone to narrowing and failure, and both inflammatory and thrombotic pathways are implicated. Platelets and monocytes are the key thrombo-inflammatory cells that arrive first at sites of vascular injury. These cells have potent interactions that recruit and activate one another, propagating thrombotic and inflammatory responses within the vessel wall. We therefore hypothesized that elevated levels of platelet-monocyte aggregates (PMA) might be associated with stenosis, and could possibly discriminate between patients with or without vein graft stenosis.
  
  
  METHODS
  Thirty-six vascular surgery patients were studied, in a stable quiescent period after infrainguinal autogenous vein graft bypasses for occlusive disease. Eighteen patients had hemodynamically significant graft stenoses confirmed by imaging, and 18 were free from stenosis. The level of PMA in whole blood was quantified after blood draw using two-color flow cytometry. Three measurements were made per sample: the basal, in-vivo level of aggregates (baseline PMA); the predisposition to spontaneously generate PMA (spontaneous PMA); and PMA generation by the addition of exogenous thrombin receptor-activating peptide (stimulated PMA). The baseline, in-vivo level of PMA was estimated by immediate flow analysis. The predisposition to spontaneously generate PMA was measured after in vitro incubation. Responsiveness to thrombin stimulation of the blood was quantified by the in vitro dose response to an exogenous thrombin receptor-activating peptide (sfllrn).
  
  
  RESULTS
  Baseline PMA levels were similar in patients with vein graft stenosis vs nonstenosis (14.8% ± 3.2 vs 10.1% ± 1.5, respectively, mean ± SEM). However, patients with stenosis showed higher spontaneous PMA levels (58.5% ± 4.5 vs 28.3% ± 4.3; P < .001) and higher stimulated PMA levels (P < .001; analysis of variance). Covariables of smoking, diabetes, statin, or antithrombotic therapy could not account for these differences.
  
  
  CONCLUSIONS
  Platelet-monocyte reactivity may play a role in the development of vein graft stenoses. Those with/without stenosis differed primarily in their threshold, or predisposition to form aggregates (spontaneous PMA), while their basal circulating levels of PMA (baseline PMA) were similar. These measurements may unmask pathologic differences in thrombo-inflammatory responsiveness that are not apparent in basal measurements. Understanding the causes and mechanisms leading to abnormal platelet-monocyte responses may improve approaches to predicting or preventing vein graft stenosis.
authors: Division of Vascular Surgery, VA Puget Sound Health Care System and the University of Washington School of Medicine, Seattle, Wash., USA. morenok@u.washington.edu
authors: Katherine
authors: K
authors: Moreno
authors: Jacqui
authors: J
authors: Murray-Wijelath
authors: Mayumi
authors: M
authors: Yagi
authors: Ted
authors: T
authors: Kohler
authors: Thomas
authors: T
authors: Hatsukami
authors: Alexander
authors: A
authors: Clowes
authors: Michael
authors: M
authors: Sobel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003251:Constriction, Pathologic; D005260:Female; D005434:Flow Cytometry; D006083:Graft Occlusion, Vascular / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D010446:Peptide Fragments / Q000494:pharmacology; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000601:surgery*; D010865:Pilot Projects; D010973:Platelet Adhesiveness / Q000187:drug effects; D010979:Platelet Function Tests; D018179:Receptors, Thrombin / Q000819:agonists / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D058017:Vascular Grafting / Q000009:adverse effects*; D014680:Veins / Q000276:immunology / Q000503:physiopathology / Q000637:transplantation*; D014861:Washington
chemical_list: D010446:Peptide Fragments; D018179:Receptors, Thrombin; C082835:thrombin receptor peptide (42-47); D013917:Thrombin