title: Leukocyte-platelet aggregates-a phenotypic characterization of different stages of peripheral arterial disease.
abstract: The formation of monocyte-platelet aggregates and neutrophil-platelet aggregates (MPA and NPA, respectively) is influenced by inflammation, but also might contribute to an exacerbation of inflammatory responses in atherosclerotic plaque. The purpose of this study was to analyze MPA and NPA proportions in regard to different stages of peripheral arterial disease (PAD). Forty-five patients with intermittent claudication (IC) (3 groups: Rutherford (R)-1, R-2, and R-3; each n = 15), 20 patients with critical limb ischemia (CLI) (Rutherford 5 (40%) and 6 (60%)), and 20 healthy controls were studied. Analyses of monocyte (Mon) subpopulations (CD14++CD16- (classical) Mon1, CD14++CD16+ (intermediate) Mon2, CD14+CD16++ (non-classical) Mon3), MPA, and NPA was performed from whole blood by flow cytometry. Controls showed an increased proportion of the Mon1 subpopulation (p < 0.001), whereas CLI patients showed a significant increase of the Mon2 subpopulation compared to controls, R-1, or R-2 patients (p < 0.0001). For the Mon3 subpopulation, CLI and R-3 patients showed an increased proportion (p < 0.05). MPA formation with the proinflammatory Mon2 and Mon3 subpopulations was increased in CLI patients (both p < 0.01). Similarly, NPA was significantly increased in CLI patients (p < 0.05). Serological markers of inflammation and procoagulation (fibrinogen [r = 0.459, p < 0.001], soluble triggering receptor expressed on myeloid cells (sTREM-1) [r = 0.237, p < 0.05] and P-Selectin [r = 0.225, p < 0.05]) correlated directly with MPA formation on the Mon2 subpopulation. We found an association of inflammatory and procoagulatory markers with increased formation of MPA on the Mon2 subpopulation. Since R-3 patients also had significantly increased MPA, one can speculate that the inflammatory burden might promote an aggravation of the disease.
authors.affiliation: a Department of Internal Medicine II , University Medical Center, Johannes Gutenberg-University , Mainz , Germany.
authors.forename: Jörn F
authors.initials: JF
authors.lastname: Dopheide
authors.affiliation: a Department of Internal Medicine II , University Medical Center, Johannes Gutenberg-University , Mainz , Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rubrech
authors.affiliation: a Department of Internal Medicine II , University Medical Center, Johannes Gutenberg-University , Mainz , Germany.
authors.forename: Amelie
authors.initials: A
authors.lastname: Trumpp
authors.affiliation: a Department of Internal Medicine II , University Medical Center, Johannes Gutenberg-University , Mainz , Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Geissler
authors.affiliation: b Department of Internal Medicine I , University Medical Center, Johannes Gutenberg-University , Mainz , Germany.
authors.forename: Geraldine C
authors.initials: GC
authors.lastname: Zeller
authors.affiliation: a Department of Internal Medicine II , University Medical Center, Johannes Gutenberg-University , Mainz , Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Bock
authors.affiliation: c Department of Cardiothoracic and Vascular Surgery, Division of Vascular Surgery , University Medical Center, Johannes-Gutenberg University , Mainz , Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Dünschede
authors.affiliation: c Department of Cardiothoracic and Vascular Surgery, Division of Vascular Surgery , University Medical Center, Johannes-Gutenberg University , Mainz , Germany.
authors.forename: Tran Tong
authors.initials: TT
authors.lastname: Trinh
authors.affiliation: c Department of Cardiothoracic and Vascular Surgery, Division of Vascular Surgery , University Medical Center, Johannes-Gutenberg University , Mainz , Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Dorweiler
authors.affiliation: a Department of Internal Medicine II , University Medical Center, Johannes Gutenberg-University , Mainz , Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Münzel
authors.affiliation: d Department of Internal Medicine III , University Medical Center, Johannes Gutenberg-University , Mainz , Germany.|e Institute for Immunology, University Medical Center, Johannes Gutenberg University , Mainz , Germany.
authors.forename: Markus P
authors.initials: MP
authors.lastname: Radsak
authors.affiliation: a Department of Internal Medicine II , University Medical Center, Johannes Gutenberg-University , Mainz , Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Espinola-Klein
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001772:Blood Cell Count; D001792:Blood Platelets / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002449:Cell Aggregation; D015897:Comorbidity; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000175:diagnosis* / Q000628:therapy; D010641:Phenotype; D017452:Receptors, IgG / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D011971:Receptors, Immunologic
keywords: Critical limb ischemia; MPA; NPA; PMN; TREM-1; monocytes; peripheral arterial disease; sTREM-1