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

Circulating leukocyte-derived microparticles predict subclinical atherosclerosis burden in asymptomatic subjects
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DOI:
10.1161/01.atv.0000249639.36915.04
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发表时间:
2006-12-01
影响因子:
8.7
通讯作者:
Tedgui, Alain
Tedgui, Alain
中科院分区:
医学1区
文献类型:
--
作者:
Chironi, Gilles;Simon, Alain;Tedgui, Alain

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目的-阐明循环微粒(MP)与临床前动脉粥样硬化的关系。方法和结果:在216名无心血管疾病的受试者中,我们分别通过Annexin V、抗GPIb、抗CD105和抗CD11a抗体包被孔捕获Annexin V阳性、血小板衍生、内皮衍生和白细胞衍生的循环微粒;(2)通过包括hsCRP在内的危险因素检测Framingham风险、代谢综合征和低度炎症;以及(3)通过超声检查颈动脉、腹主动脉和股动脉来评估亚临床动脉粥样硬化。斑块数目为0~3个,斑块负荷分为0~1或2~3个斑块病变。有中到高度Framingham危险(P<0.001)、代谢综合征(P<0.01)、高C反应蛋白(P<0.05)或2-3位点疾病(P<0.01)时,白细胞来源的MP水平较高,且与代谢综合征组分(P<0.001)、纤维蛋白原水平(P<0.001)和病变部位数(P<0.01)呈正相关。在多变量分析中,2-3位点疾病与白细胞来源的MP水平(P<0.05)、Framingham风险(P<0.001)和代谢综合征(P<0.01)独立相关。结论:在有亚临床动脉粥样硬化超声证据的受试者中,白细胞来源的MP与CD11a的亲和力增加,为动脉粥样硬化的研究提供了新的方向。
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.