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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2775.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Circulating Leukocyte-Derived Microparticles Predict Subclinical Atherosclerosis Burden in Asymptomatic Subjects

Gilles Chironi; Alain Simon; Bénédicte Hugel; Muriel Del Pino; Jérôme Gariepy; Jean-Marie Freyssinet; Alain Tedgui

From AP-HP, Centre Hospitalier HEGP–Broussais, (G.C., A.S., M.D.P., J.G.), Centre de Médecine Préventive Cardiovasculaire, Paris, France; Université René Descartes (G.C., A.S., M.D.P., J.G.), Paris, France; Unité INSERM U770 (B.H., J.M.F.), Hôpital Bicêtre, Le Kremlin Bicêtre; Institut d’Hématologie et d’Immunologie, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France; Unité INSERM U689 & Institut Fédératif de Recherche Circulation (A.T.), Paris, France.

Correspondence to Pr Alain Simon, Centre de Médecine Préventive Cardiovasculaire, 96 rue Didot, F-75674 Paris, France. E-mail alain.simon{at}brs.aphp.fr

Objective— To clarify circulating microparticles (MP) relationships with preclinical atherosclerosis.

Methods and Results— In 216 subjects without cardiovascular disease, we assessed: (1) annexin V-positive, platelet-derived, endothelium-derived and leukocyte-derived circulating MP by capture on annexin V, anti-GPIb, anti-CD105, and anti-CD11a antibody-coated wells, respectively; (2) Framingham risk, metabolic syndrome, and low-grade inflammation by risk factors measurement including hsCRP; and (3) subclinical atherosclerosis by ultrasound examination of carotid, abdominal aorta, and femoral arteries. Number of sites with plaque ranged from 0 to 3 and plaque burden was classified into 0 to 1 or 2 to 3 sites disease. Leukocyte-derived MP level was higher in the presence than in the absence of moderate to high Framingham risk (P<0.05), metabolic syndrome (P<0.01), high C-reactive protein (CRP) (P<0.05), or 2- to 3-sites disease (P<0.01), and correlated positively with number of metabolic syndrome components (P<0.001), tertiles of fibrinogen (P<0.001), and number of diseased sites (P<0.01). In multivariate analysis, 2- to 3-sites disease was independently associated with leukocyte-derived MP level (P<0.05), Framingham risk (P<0.001), and metabolic syndrome (P<0.01). None of the other MP types correlated with risk markers or atherosclerosis.

Conclusions— Leukocyte-derived MP, identified by affinity for CD11a, are increased in subjects with ultrasound evidence of subclinical atherosclerosis, unveiling new directions for atherosclerosis research.

Circulating leukocyte-derived microparticles (MP) were related to Framingham risk, metabolic syndrome, CRP, and presence and extent of preclinical atherosclerosis in 216 primary prevention subjects. These relationships of leukocyte-derived MP with atherosclerosis were independent of all risk markers, leukocyte count, and concomitant drugs. These data unveil new directions for atherosclerosis research.

Key Words: atherosclerosis • leukocytes • microparticles • risk factors • ultrasonic diagnosis

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