Association of plasma levels of F11 receptor/junctional adhesion molecule-A (F11R/JAM-A) with human atherosclerosis
Association of plasma levels of F11 receptor/junctional adhesion molecule-A (F11R/JAM-A) with human atherosclerosis
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DOI：
10.1016/j.jacc.2007.05.051
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发表时间：
2007-10-30
影响因子：
24
通讯作者：
Marmur, Jonathan D.
中科院分区：
文献类型：
--
作者：
Cavusoglu, Erdal;Kornecki, Elizabeth;Marmur, Jonathan D.
目的探讨F11受体（F11 R）与血管疾病的关系。F11 R是一种在体外被鉴定为血小板粘附于血管内皮细胞表面的关键分子。已知F11 R在血小板和内皮细胞中表达，最近有报道称其在动脉粥样硬化斑块中过度表达。在退伍军人管理局医疗中心进行冠状动脉造影的389例已知或疑似冠心病（CAD）男性患者中，测量了F11 R水平，沿着许多其他生物标志物。（CAD血管造影评分为0），轻度至中度疾病（评分为1 - 3分），和严重疾病（评分4 - 6）的F11 R血浆水平中位数分别为38.6 pg/ml（平均260 +/- 509.6 pg/ml）、45.2 pg/ml（平均395.3 +/- 752.7 pg/ml）和105.8 pg/ml（平均629 831.7 pg/ml）（p = 0.03）。通过多变量分析，与CAD评分独立相关的变量为年龄、高脂血症、慢性肾功能不全、左心室功能和血浆F11 R水平。F11 R是唯一与CAD评分独立相关的生物标志物。与先前报道的肿瘤坏死因子（TNF）-α对培养的内皮细胞中F11 R表达的影响一致，F11 R水平与血浆TNF-α水平密切相关（r = 0.84; p < 0.0001）。由于其与血浆TNF-α的强相关性，F11 R可能是炎症对血管壁影响的重要介质。阻断F11 R的策略可能代表了治疗人类动脉粥样硬化的新方法。
Objectives The purpose of this study was to determine the association of the F11 receptor (F11R) with human vascular disease. Background A molecule identified as critical for platelet adhesion to a cytokine-inflamed endothelial surface in vitro is F11R. The F11R is known to be expressed in platelets and endothelium and reported recently to be overexpressed in atherosclerotic plaques.Methods A novel enzyme-linked immunosorbent assay was developed for the measurement of soluble F11R in human plasma. The F11R levels, along with a number of other biomarkers, were measured in 389 male patients with known or suspected coronary artery disease (CAD) undergoing coronary angiography at a Veterans Administration Medical Center.Results Patients with normal or nonobstructive disease (CAD angiographic score of 0), mild-to-moderate disease (score of I to 3), and severe disease (score of 4 to 6) had median F11R plasma levels of 38.6 pg/ml (mean 260 +/- 509.6 pg,/ml), 45.2 pg/ml (mean 395.3 +/- 752.7 pg/ml), and :105.8 pg/ml (mean 629 831.7 pg/ml), respectively (p = 0.03). By multivariate analysis, the variables independently associated with CAD score were age, hyperlipidemia, chronic renal insufficiency, left ventricular function, and plasma F11R levels. The F11R was the only biomarker that was independently associated with CAD score. Consistent with the previously reported effects of tumor necrosis factor (TNF)-alpha on F11R expression in cultured endothelial cells, F11R levels correlated strongly with plasma TNF-alpha levels (r = 0.84; p < 0.0001).Conclusions Plasma F11R is independently associated with the presence and severity of angiographically defined CAD. By virtue of its strong correlation to plasma TNF-alpha, F11R may be an important mediator of the effects of inflammation on the vessel wall. Strategies that block F11R may represent a novel approach to the treatment of human atherosclerosis.