Increased platelet reactivity is associated with circulating platelet-monocyte complexes and macrophages in human
Bert Rutten1, Claudia Tersteeg2, Joyce E P Vrijenhoek3
1Laboratory of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, the Netherlands.
Insights
Increased platelet reactivity correlates with higher levels of platelet-monocyte complexes and macrophages in atherosclerotic plaques, suggesting a link between platelet activation and disease progression.
Area of Science:
- Cardiovascular Biology
- Immunology
- Atherosclerosis Research
Background:
- Platelet activation, monocyte binding, and infiltration are key drivers of atherosclerotic plaque development.
- Understanding the interplay between platelets and monocytes is crucial for targeting atherosclerosis.
Purpose of the Study:
- To investigate the association between platelet reactivity and circulating platelet-monocyte complexes (PMCs).
- To determine if platelet reactivity correlates with macrophage levels within human atherosclerotic carotid plaques.
Main Methods:
- Platelet reactivity was measured via P-selectin expression after adenosine diphosphate (ADP) stimulation in two cohorts.
- Circulating PMCs were assessed using flow cytometry.
- Macrophage infiltration in carotid plaques was evaluated through histological analysis.
Main Results:
- Higher platelet reactivity was observed in patients with elevated PMCs (P<0.001).
- Increased platelet reactivity was also associated with higher macrophage levels in atherosclerotic plaques (P=0.02).
- These associations remained significant after adjusting for clinical factors.
Conclusions:
- Platelet reactivity to ADP is significantly associated with circulating platelet-monocyte complexes.
- Elevated platelet reactivity correlates with increased macrophage infiltration in human atherosclerotic carotid plaques.
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.
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