4.7 Article

Circulating leukocyte-derived microparticles predict subclinical atherosclerosis burden in asymptomatic subjects

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LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.ATV.0000249639.36915.04

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atherosclerosis; leukocytes; microparticles; risk factors; ultrasonic diagnosis

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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.

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