PLoS ONE (Jan 2014)

Increased platelet reactivity is associated with circulating platelet-monocyte complexes and macrophages in human atherosclerotic plaques.

  • Bert Rutten,
  • Claudia Tersteeg,
  • Joyce E P Vrijenhoek,
  • Thijs C van Holten,
  • Ellen H A M Elsenberg,
  • Elske M Mak-Nienhuis,
  • Gert Jan de Borst,
  • J Wouter Jukema,
  • Nico H J Pijls,
  • Johannes Waltenberger,
  • Anton Jan van Zonneveld,
  • Frans L Moll,
  • Elizabeth McClellan,
  • Andrew Stubbs,
  • Gerard Pasterkamp,
  • Imo Hoefer,
  • Philip G de Groot,
  • Mark Roest

DOI
https://doi.org/10.1371/journal.pone.0105019
Journal volume & issue
Vol. 9, no. 8
p. e105019

Abstract

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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.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).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.Platelet reactivity towards ADP is associated with levels of PMCs and macrophages in human atherosclerotic carotid plaques.