title: Increased platelet reactivity is associated with circulating platelet-monocyte complexes and macrophages in human atherosclerotic plaques.
abstract: OBJECTIVE
  Platelet reactivity, platelet binding to monocytes and monocyte infiltration play a detrimental role in atherosclerotic plaque progression. We investigated whether platelet reactivity was associated with levels of circulating platelet-monocyte complexes (PMCs) and macrophages in human atherosclerotic carotid plaques.
  
  
  METHODS
  Platelet reactivity was determined by measuring platelet P-selectin expression after platelet stimulation with increasing concentrations of adenosine diphosphate (ADP), in two independent cohorts: the Circulating Cells cohort (n = 244) and the Athero-Express cohort (n = 91). Levels of PMCs were assessed by flow cytometry in blood samples of patients who were scheduled for percutaneous coronary intervention (Circulating Cells cohort). Monocyte infiltration was semi-quantitatively determined by histological examination of atherosclerotic carotid plaques collected during carotid endarterectomy (Athero-Express cohort).
  
  
  RESULTS
  We found increased platelet reactivity in patients with high PMCs as compared to patients with low PMCs (median (interquartile range): 4153 (1585-11267) area under the curve (AUC) vs. 9633 (3580-21565) AUC, P<0.001). Also, we observed increased platelet reactivity in patients with high macrophage levels in atherosclerotic plaques as compared to patients with low macrophage levels in atherosclerotic plaques (mean ± SD; 8969 ± 3485 AUC vs. 7020 ± 3442 AUC, P = 0.02). All associations remained significant after adjustment for age, sex and use of drugs against platelet activation.
  
  
  CONCLUSIONS
  Platelet reactivity towards ADP is associated with levels of PMCs and macrophages in human atherosclerotic carotid plaques.
authors.affiliation: Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Bert
authors.initials: B
authors.lastname: Rutten
authors.affiliation: Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, the Netherlands; Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Claudia
authors.initials: C
authors.lastname: Tersteeg
authors.affiliation: Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, the Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands.
authors.forename: Joyce E P
authors.initials: JE
authors.lastname: Vrijenhoek
authors.affiliation: Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Thijs C
authors.initials: TC
authors.lastname: van Holten
authors.affiliation: Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Ellen H A M
authors.initials: EH
authors.lastname: Elsenberg
authors.affiliation: Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, the Netherlands; Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Elske M
authors.initials: EM
authors.lastname: Mak-Nienhuis
authors.affiliation: Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: de Borst
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
authors.affiliation: Department of Cardiology, Catharina Hospital, Eindhoven, the Netherlands.
authors.forename: Nico H J
authors.initials: NH
authors.lastname: Pijls
authors.affiliation: Department for Cardiology, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Waltenberger
authors.affiliation: Department of Nephrology and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Anton Jan
authors.initials: AJ
authors.lastname: van Zonneveld
authors.affiliation: Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.affiliation: Department of Bioinformatics, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McClellan
authors.affiliation: Department of Bioinformatics, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Andrew
authors.initials: A
authors.lastname: Stubbs
authors.affiliation: Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.affiliation: Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Imo
authors.initials: I
authors.lastname: Hoefer
authors.affiliation: Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.affiliation: Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Roest
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000503:physiopathology