Cavusoglu Erdal, Kornecki Elizabeth, Sobocka Malgorzata B, Babinska Anna, Ehrlich Yigal H, Chopra Vineet, Yanamadala Sunitha, Ruwende Cyril, Salifu Moro O, Clark Luther T, Eng Calvin, Pinsky David J, Marmur Jonathan D
Division of Cardiology, Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, New York 11203-2098, USA.
J Am Coll Cardiol. 2007 Oct 30;50(18):1768-76. doi: 10.1016/j.jacc.2007.05.051.
The purpose of this study was to determine the association of the F11 receptor (F11R) with human vascular disease.
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.
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.
Patients with normal or nonobstructive disease (CAD angiographic score of 0), mild-to-moderate disease (score of 1 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).
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.
本研究旨在确定F11受体（F11R）与人类血管疾病之间的关联。
一种在体外被确定为对血小板黏附于细胞因子炎症内皮表面至关重要的分子是F11R。已知F11R在血小板和内皮中表达，且最近报道其在动脉粥样硬化斑块中过度表达。
开发了一种新型酶联免疫吸附测定法用于检测人血浆中的可溶性F11R。在一家退伍军人管理局医疗中心，对389名已知或疑似患有冠状动脉疾病（CAD）且正在接受冠状动脉造影的男性患者测定了F11R水平以及其他一些生物标志物。
患有正常或非阻塞性疾病（CAD血管造影评分为0）、轻度至中度疾病（评分为1至3）和重度疾病（评分为4至6）的患者，其血浆F11R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有年龄、高脂血症、慢性肾功能不全、左心室功能和血浆F11R水平。F11R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对培养内皮细胞中F11R表达的影响一致，F11R水平与血浆TNF-α水平密切相关（r = 0.84；p < 0.0001）。
血浆F11R与血管造影定义的CAD的存在和严重程度独立相关。由于其与血浆TNF-α的强相关性，F11R可能是炎症对血管壁影响的重要介质。阻断F11R的策略可能代表一种治疗人类动脉粥样硬化的新方法。
