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Published on: February 20, 2015
Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques
Aurélie S Leroyer1, Hirotaka Isobe, Guy Lesèche
1INSERM Cardiovascular Research Center Lariboisière, Paris, France.
Objectives:
In this study, we evaluated the cellular origins and thrombogenic potential of microparticles.
Background:
Human atherosclerotic plaques contain submicron vesicles (microparticles) released during cell activation or apoptosis.
Methods:
Microparticles were purified from plaques and platelet-free plasma from 26 patients undergoing carotid endarterectomy. Flow cytometry analysis revealed the presence of large amounts of microparticles in plaques but not in healthy vessels.
Results:
Most plaque microparticles originated from leukocytes, of which 29 +/- 5% were macrophages, 15 +/- 3% lymphocytes, and 8 +/- 1% granulocytes. Plaques microparticles also derived from erythrocytes (27 +/- 4%), smooth muscle (13 +/- 4%) and endothelial cells (8 +/- 2%), but not from platelets. Plaques from asymptomatic and symptomatic patients showed no differences in microparticle origins. Microparticles were at least 200-fold more concentrated in plaque than in plasma. Plasma microparticles were primarily platelet-derived in contrast with those of plaque and showed no smooth muscle cell origin. Both plaque and plasma microparticles exposed tissue factor and generated thrombin, but this activity was twice as high in microparticles isolated from plaques, reflecting the thrombogenic contribution of the individual classes of microparticles.
Conclusions:
These results demonstrate that microparticles are more abundant and more thrombogenic in human atherosclerotic plaques than in plasma. The different cellular origins of plaque and plasma microparticles might explain the increased thrombogenic activity of plaque microparticles.
Insights
Microparticles are more concentrated and clot-forming in atherosclerotic plaques than in blood plasma. Leukocytes are the main source of these plaque microparticles, contributing to their higher thrombogenic potential.
Area of Science:
- Cardiovascular Biology
- Hematology
- Cellular Biology
Background:
- Human atherosclerotic plaques contain submicron vesicles called microparticles, released during cell activation or apoptosis.
- Microparticles are implicated in the pathogenesis of atherosclerosis.
Purpose of the Study:
- To investigate the cellular origins of microparticles within human atherosclerotic plaques.
- To evaluate the thrombogenic potential of plaque-derived microparticles compared to plasma microparticles.
Main Methods:
- Purification of microparticles from atherosclerotic plaques and platelet-free plasma of patients undergoing carotid endarterectomy.
- Flow cytometry analysis to determine the cellular origin and concentration of microparticles.
- Assessment of tissue factor exposure and thrombin generation by microparticles.
Main Results:
- Microparticles were significantly more concentrated (over 200-fold) in plaques than in plasma.
- Leukocytes (macrophages, lymphocytes, granulocytes), erythrocytes, smooth muscle cells, and endothelial cells were identified as origins of plaque microparticles; platelets were not.
- Plasma microparticles were predominantly platelet-derived.
- Both plaque and plasma microparticles exposed tissue factor and generated thrombin, with plaque microparticles showing twice the activity.
Conclusions:
- Microparticles are more abundant and possess greater thrombogenic potential in atherosclerotic plaques compared to plasma.
- The distinct cellular origins of plaque and plasma microparticles likely contribute to the heightened thrombogenicity observed in plaques.
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