Circulating Microparticles in Patients with Symptomatic Carotid Disease Are Related to Embolic Plaque Activity and
Neghal Kandiyil1,2, Shane T MacSweeney3, Stan Heptinstall4
1Radiological Sciences in the Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, United Kingdom, neghal.kandiyil@uhl-tr.nhs.uk.
Background And Purpose:
In order to assess the association of microparticles derived from activated platelets (PMP) or endothelial cells (EMP) with risk markers for recurrent embolic events in patients with symptomatic carotid artery disease, we studied the associations between PMP/EMP and three risk markers: plaque haemorrhage (PH), micro-embolic signals and cerebral diffusion abnormalities.
Methods:
Patients with recently symptomatic high-grade carotid artery stenosis (60-99%, 42 patients, 31 men; mean age 75 ± 8 years) and 30 healthy volunteers (HV, 11 men; mean age 56 ± 12 years) were prospectively recruited. Patients were characterised by carotid magnetic resonance imaging (presence of PH [MRI PH]), brain diffusion MRI (cerebral ischaemia [DWI+]) and transcranial Doppler ultrasound (micro-embolic signals [MES+]). PMP and EMP were classified by flow cytometry and expressed as log-transformed counts per microlitre.
Results:
MES+ patients (n = 18) had elevated PMP (MES+ 9.61 ± 0.57) compared to HV (8.80 ± 0.73; p < 0.0001) and to MES- patients (8.55 ± 0.85; p < 0.0001). Stroke patients had elevated PMP (9.49 ± 0.64) and EMP (6.13 ± 1.0) compared to non-stroke patients (PMP 8.81 ± 0.73, p = 0.026, EMP 5.52 ± 0.65, p = 0.011) and HV (PMP 8.80 ± 0.73, p = 0.007, and EMP 5.44 ± 0.47, p = 0.006). DWI+ patients (n = 16) showed elevated PMP (DWI+ 9.53 ± 0.64; vs. HV, p = 0.002) and EMP (DWI+ 5.91 ± 0.99 vs. HV 5.44 ± 0.47; p = 0.037). Only PMP but not EMP were higher in DWI+ versus DWI- patients (8.67 ± 0.90; p = 0.002). No association was found between PMP and EMP with MRI PH.
Conclusions:
PMP and EMP were associated with stroke and recent cerebrovascular events (DWI+) but only PMP were also associated with ongoing (MES+) thrombo-embolic activity suggesting a differential biomarker potential for EMP to index cerebral ischaemia while PMP may predict on-going thrombo-embolic activity.
Insights
Platelet-derived microparticles (PMP) and endothelial cell-derived microparticles (EMP) are linked to stroke risk. PMP indicate ongoing embolic activity, while EMP may reflect cerebral ischemia in carotid artery disease.
Area of Science:
- Cardiovascular Research
- Biomarker Discovery
- Neuroscience
Background:
- Symptomatic carotid artery disease poses a risk for recurrent embolic events.
- Microparticles derived from activated platelets (PMP) and endothelial cells (EMP) are implicated in vascular pathology.
Purpose of the Study:
- To assess the association of PMP and EMP with risk markers for recurrent embolic events in patients with symptomatic carotid artery disease.
- To investigate the relationship between PMP/EMP and plaque hemorrhage, micro-embolic signals, and cerebral diffusion abnormalities.
Main Methods:
- Prospective study of 42 patients with symptomatic high-grade carotid artery stenosis and 30 healthy volunteers.
- Carotid MRI for plaque hemorrhage (PH), brain diffusion MRI for cerebral ischemia (DWI+), and transcranial Doppler ultrasound for micro-embolic signals (MES+).
- PMP and EMP quantified using flow cytometry.
Main Results:
- MES+ patients exhibited elevated PMP compared to healthy volunteers and MES- patients.
- Stroke patients showed elevated PMP and EMP compared to non-stroke patients and healthy volunteers.
- DWI+ patients had elevated PMP and EMP; PMP were specifically higher in DWI+ versus DWI- patients. No association found between PMP/EMP and MRI PH.
Conclusions:
- PMP and EMP are associated with stroke and recent cerebrovascular events (DWI+).
- PMP are associated with ongoing thrombo-embolic activity (MES+).
- EMP may serve as a biomarker for cerebral ischemia, while PMP may predict ongoing thrombo-embolic activity.
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