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CLINICAL RESEARCH: ATHEROSCLEROSIS

Cellular Origins and Thrombogenic Activity of Microparticles Isolated From Human Atherosclerotic Plaques

Aurélie S. Leroyer, BSc^_*, Hirotaka Isobe, PhD, Guy Lesèche, MD, PhD, Yves Castier, MD, PhD, Michel Wassef, PhD, Ziad Mallat, MD, PhD^_*, Bernd R. Binder, MD, PhD, Alain Tedgui, PhD^_* and Chantal M. Boulanger, PhD^_*,_*

^_* INSERM Cardiovascular Research Center Lariboisière, Paris, France
Department of Vascular Biology and Thrombosis Research, Medical University, Vienna, Austria
Vascular Surgery Department, Beaujon Hospital, Clichy, France
Lariboisière Hospital, Paris, France.

Manuscript received April 24, 2006; revised manuscript received September 8, 2006, accepted October 9, 2006.

^_* Reprint requests and correspondence: Dr. Chantal M. Boulanger, INSERM CRC Lariboisière, 41 bd Chapelle, 75475 Paris, France. (Email: chantal.boulanger{at}larib.inserm.fr).

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.

Abbreviations and Acronyms   IgG = immunoglobulin G   MPs = microparticles   PFP = platelet-free plasma   RBC = red blood cell   SMA = smooth muscle cell actin   SMC = smooth muscle cell   TF = tissue factor   TGA = thrombin-generating activity

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