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

被引：10

作者：

Rutten, Bert ^{[1
]}

Tersteeg, Claudia ^{[1
,2
]}

Vrijenhoek, Joyce E. P. ^{[2
,3
,4
]}

van Holten, Thijs C. ^{[1
]}

Elsenberg, Ellen H. A. M. ^{[2
]}

Mak-Nienhuis, Elske M. ^{[1
,2
]}

de Borst, Gert Jan ^{[3
]}

Jukema, J. Wouter ^{[5
]}

Pijls, Nico H. J. ^{[6
]}

Waltenberger, Johannes ^{[7
]}

van Zonneveld, Anton Jan ^{[8
,9
]}

Moll, Frans L. ^{[3
]}

McClellan, Elizabeth ^{[10
]}

Stubbs, Andrew ^{[10
]}

Pasterkamp, Gerard ^{[2
]}

Hoefer, Imo ^{[2
]}

de Groot, Philip G. ^{[1
]}

Roest, Mark ^{[1
]}

机构：

[1] Univ Med Ctr Utrecht, Lab Clin Chem & Hematol, Utrecht, Netherlands

[2] Univ Med Ctr Utrecht, Lab Expt Cardiol, Utrecht, Netherlands

[3] Univ Med Ctr Utrecht, Dept Vasc Surg, Utrecht, Netherlands

[4] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands

[5] Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands

[6] Catharina Hosp, Dept Cardiol, Eindhoven, Netherlands

[7] Maastricht Univ, Dept Cardiol, Med Ctr, Maastricht, Netherlands

[8] Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands

[9] Leiden Univ, Med Ctr, Einthoven Lab Expt Vasc Med, Leiden, Netherlands

[10] Erasmus Univ, Med Ctr, Dept Bioinformat, Rotterdam, Netherlands

来源：

PLOS ONE | 2014年 / 9卷 / 08期

关键词：

P-SELECTIN; EXPRESSION; ENDARTERECTOMY; CLOPIDOGREL; ADHESION; ACTIVATION; DEFICIENT; TRIGGERS; PROTEIN; ARREST;

D O I：

10.1371/journal.pone.0105019

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：8

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