El-Omar Magdi M, Islam Naziba, Broekman M Johan, Drosopoulos Joan H F, Roa Donald C, Lorin Jeffrey D, Sedlis Steven P, Olson Kim E, Pulte E Dianne, Marcus Aaron J
Department of Medicine-Cardiology, New York University Medical School, New York, NY, USA.
Thromb Res. 2005;116(3):199-206. doi: 10.1016/j.thromres.2004.11.024. Epub 2004 Dec 21.
CD39 (NTPDase1), an endothelial cell membrane glycoprotein, is the predominant ATP diphosphohydrolase (ATPDase) in vascular endothelium. It hydrolyses both triphosphonucleosides and diphosphonucleosides at comparable rates, thus terminating platelet aggregation and recruitment responses to ADP and other platelet agonists. This occurs even when nitric oxide (NO) formation and prostacyclin production are inhibited. Thus, CD39 represents the main control system for platelet reactivity. Reduced or deficient local ecto-nucleotidase activity may predispose to development of vascular disease. Based on data in animal models and in vitro, CD39 constitutes a new therapeutic modality for vascular disease with a novel and unique mode of action.
Lymphocytes were isolated from 46 patients with angiographically proven coronary artery disease (CAD) as well as from matched healthy control subjects. Ectonucleotidase ADPase and ATPase activities (prototypical for the ATPDase activity of endothelial cells) were measured using established radio-TLC procedures.
In the patients, a decreased ratio of ADPase to ATPase activities (from 1.26 to 1.04) was observed despite increases in both ADPase and ATPase activities. Coronary artery disease was the only independent predictor of a difference in the ADPase/ATPase activity ratio by multivariate linear regression analysis (P=0.0035). This altered ADPase/ATPase activity ratio in patients may represent a reduction in endogenous defense systems against platelet-driven thrombotic events. These data may identify a population of patients with excessive platelet reactivity in their circulation. Increased generation of prothrombotic ADP in these patients implies a potential benefit from therapeutic intervention with soluble forms of CD39.
CD39（NTPDase1）是一种内皮细胞膜糖蛋白，是血管内皮中主要的ATP二磷酸水解酶（ATPDase）。它以相似的速率水解三磷酸核苷和二磷酸核苷，从而终止血小板对ADP和其他血小板激动剂的聚集和募集反应。即使在一氧化氮（NO）生成和前列环素产生受到抑制时，这种情况也会发生。因此，CD39代表了血小板反应性的主要控制系统。局部外切核苷酸酶活性降低或缺乏可能易患血管疾病。基于动物模型和体外数据，CD39构成了一种具有新颖独特作用方式的血管疾病新治疗模式。
从46例经血管造影证实患有冠状动脉疾病（CAD）的患者以及匹配的健康对照受试者中分离淋巴细胞。使用既定的放射性薄层色谱法测量外切核苷酸酶ADP酶和ATP酶活性（内皮细胞ATPDase活性的典型代表）。
在患者中，尽管ADP酶和ATP酶活性均增加，但观察到ADP酶与ATP酶活性之比降低（从1.26降至1.04）。通过多变量线性回归分析，冠状动脉疾病是ADP酶/ATP酶活性比差异的唯一独立预测因子（P = 0.0035）。患者中这种改变的ADP酶/ATP酶活性比可能代表针对血小板驱动的血栓形成事件的内源性防御系统的降低。这些数据可能识别出循环中血小板反应性过高患者群体。这些患者中促血栓形成性ADP生成增加意味着可溶性形式的CD39治疗干预可能有益。
