Increased Platelet Reactivity Is Associated with Circulating Platelet-Monocyte Complexes and Macrophages in Human Atherosclerotic Plaques

B Rutten; C Tersteeg; JEP Vrijenhoek; TC van Holten; EHAM Elsenberg; EM Mak-Nienhuis; GJ de Borst; JW Jukema; NHJ Pijls; J Waltenberger; AJ Zonneveld; FL Moll; E McClellan; Andrew Stubbs; G Pasterkamp; I Hoefer; PG de Groot; M Roest

doi:10.1371/journal.pone.0105019

Increased Platelet Reactivity Is Associated with Circulating Platelet-Monocyte Complexes and Macrophages in Human Atherosclerotic Plaques

B Rutten, C Tersteeg, JEP Vrijenhoek, TC van Holten, EHAM Elsenberg, EM Mak-Nienhuis, GJ de Borst, JW Jukema, NHJ Pijls, J Waltenberger, AJ Zonneveld, FL Moll, E McClellan, Andrew Stubbs, G Pasterkamp, I Hoefer, PG de Groot, M Roest

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

Original language	Undefined/Unknown
Number of pages	8
Journal	PLoS One (print)
Volume	9
Issue number	8
DOIs	https://doi.org/10.1371/journal.pone.0105019
Publication status	Published - 2014

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Rutten, B., Tersteeg, C., Vrijenhoek, JEP., van Holten, TC., Elsenberg, EHAM., Mak-Nienhuis, EM., de Borst, GJ., Jukema, JW., Pijls, NHJ., Waltenberger, J., Zonneveld, AJ., Moll, FL., McClellan, E., Stubbs, A., Pasterkamp, G., Hoefer, I., de Groot, PG., & Roest, M. (2014). Increased Platelet Reactivity Is Associated with Circulating Platelet-Monocyte Complexes and Macrophages in Human Atherosclerotic Plaques. PLoS One (print), 9(8). https://doi.org/10.1371/journal.pone.0105019

@article{4b52e1707dc14ebc9ed86ec045aba85c,

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. Conclusion: Platelet reactivity towards ADP is associated with levels of PMCs and macrophages in human atherosclerotic carotid plaques.",

author = "B Rutten and C Tersteeg and JEP Vrijenhoek and {van Holten}, TC and EHAM Elsenberg and EM Mak-Nienhuis and {de Borst}, GJ and JW Jukema and NHJ Pijls and J Waltenberger and AJ Zonneveld and FL Moll and E McClellan and Andrew Stubbs and G Pasterkamp and I Hoefer and {de Groot}, PG and M Roest",

year = "2014",

doi = "10.1371/journal.pone.0105019",

language = "Undefined/Unknown",

volume = "9",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "8",

}

Rutten, B, Tersteeg, C, Vrijenhoek, JEP, van Holten, TC, Elsenberg, EHAM, Mak-Nienhuis, EM, de Borst, GJ, Jukema, JW, Pijls, NHJ, Waltenberger, J, Zonneveld, AJ, Moll, FL, McClellan, E, Stubbs, A, Pasterkamp, G, Hoefer, I, de Groot, PG & Roest, M 2014, 'Increased Platelet Reactivity Is Associated with Circulating Platelet-Monocyte Complexes and Macrophages in Human Atherosclerotic Plaques', PLoS One (print), vol. 9, no. 8. https://doi.org/10.1371/journal.pone.0105019

TY - JOUR

T1 - Increased Platelet Reactivity Is Associated with Circulating Platelet-Monocyte Complexes and Macrophages in Human Atherosclerotic Plaques

AU - Rutten, B

AU - Tersteeg, C

AU - Vrijenhoek, JEP

AU - van Holten, TC

AU - Elsenberg, EHAM

AU - Mak-Nienhuis, EM

AU - de Borst, GJ

AU - Jukema, JW

AU - Pijls, NHJ

AU - Waltenberger, J

AU - Zonneveld, AJ

AU - Moll, FL

AU - McClellan, E

AU - Stubbs, Andrew

AU - Pasterkamp, G

AU - Hoefer, I

AU - de Groot, PG

AU - Roest, M

PY - 2014

Y1 - 2014

N2 - 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. Conclusion: Platelet reactivity towards ADP is associated with levels of PMCs and macrophages in human atherosclerotic carotid plaques.

AB - 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. Conclusion: Platelet reactivity towards ADP is associated with levels of PMCs and macrophages in human atherosclerotic carotid plaques.

U2 - 10.1371/journal.pone.0105019

DO - 10.1371/journal.pone.0105019

M3 - Article

SN - 1932-6203

VL - 9

JO - PLoS ONE

JF - PLoS ONE

IS - 8

ER -