Elevated levels of VE-cadherin-positive endothelial microparticles in patients with type 2 diabetes mellitus and coronary artery disease
Elevated levels of VE-cadherin-positive endothelial microparticles in patients with type 2 diabetes mellitus and coronary artery disease
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DOI：
10.1016/j.jacc.2005.02.047
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发表时间：
2005-05-17
影响因子：
24
通讯作者：
Jinnouchi, H
中科院分区：
文献类型：
--
作者：
Koga, H;Sugiyama, S;Jinnouchi, H
本研究的目的是检查CD 144-EMP是否（内皮衍生的微粒）可用作内皮细胞（EC）功能障碍的特异性标志物，并可用于确定循环CD 144-EMP的血浆水平是否可预测2型糖尿病（DM）患者的冠状动脉疾病（CAD）。然而，EC功能障碍的定量评估尚未在临床上建立。内皮衍生的微粒是响应于细胞功能障碍和/或损伤而从EC表面产生的小的膜脱落囊泡。糖尿病是已知的EC功能障碍和加速atherosclerosis.METHODS我们的特点EMP使用抗CD 144（VE钙粘蛋白）抗体在各种动脉粥样硬化相关的细胞和研究之间的关联CD 144阳性微粒的水平和过氧化氢诱导的EC损伤和乙酰胆碱诱导的冠状动脉血管运动。此外，我们评估了血浆中的CD 144-EMP水平与糖尿病患者和非DM。结果，我们证明，CD 144阳性微粒是来自人类EC的选择性。CD 144-EMP水平反映了过氧化氢对EC的损伤程度和对内皮依赖性冠脉舒张功能的损害程度（p < 0.01）。DM患者血浆CD 144-EMP水平显著高于非DM患者（P < 0.001）。在DM患者中，相对于所有其他传统危险因素，CD 144-EMP水平升高是CAD最显著的危险因素（比值比[OR] 3.5，95%置信区间[CI] 1.8至6.9，p < 0.001）。结论人血浆中存在CD 144阳性EMP，血浆CD 144-EMP水平可作为EC功能障碍和/或损伤的一个临床特异性定量指标。测量CD 144-EMP，通过提供EC功能障碍的定量评估，可能有助于识别CAD风险增加的DM患者。(c)2005年，美国心脏病学会基金会。
OBJECTIVES The purpose of this study was to examine whether CD144-EMP (endothelium-derived microparticles) is useful as a specific marker of endothelial cell (EC) dysfunction and to determine whether plasma levels of circulating CD144-EMP predicted coronary artery disease (CAD) in patients with type 2 diabetes mellitus (DM).BACKGROUND Endothelial cell dysfunction is involved in atherogenesis; however, the quantitative assessment of EC dysfunction has yet to be established clinically. Endothelium-derived microparticles are small, membrane-shed vesicles that are generated from the EC surface in response to cellular dysfunction and/or injury. Diabetes mellitus is known to be associated with EC dysfunction and accelerated atherosclerosis.METHODS We characterized EMP using anti-CD144 (VE-Cadherin) antibody in various atherosclerosis-related cells and investigated the association between the levels of CD144-positive microparticles and hydrogen-peroxide-induced EC injury and acetylcholine-induced coronary vasomotion. Furthermore, we evaluated plasma CD144-EMP levels in patients with and without DM.RESULTS We demonstrated that CD144-positive microparticles were derived selectively from human EC. The levels of CD144-EMP reflected the degree of in vitro hydrogen-peroxide-induced EC injury and impairment of in vivo endothelium-dependent coronary vasodilation (p < 0.01). Plasma CD144-EMP levels were increased significantly in DM patients compared with patients without DM (p < 0.001). In DM patients, the elevated levels of CD144-EMP were the most significant risk factor for CAD relative to all other traditional risk factors (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.8 to 6.9, p < 0.001). Notably, plasma CD144-EMP identified a subpopulation of established CAD patients in DM subjects without typical anginal symptoms (OR 10.6, 95% CI 3.9 to 29.5, p < 0.001).CONCLUSIONS The CD144-positive EMP exist in human plasma, and plasma CD144-EMP levels can be a clinically specific and quantitative marker of EC dysfunction and/or injury. Measurement of CD144-EMP, by providing a quantitative assessment of EC dysfunction, may be useful for identifying DM patients with increased risk of CAD. (c) 2005 by the American College of Cardiology Foundation.