期刊
THROMBOSIS RESEARCH
卷 116, 期 3, 页码 199-206出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.thromres.2004.11.024
关键词
cardiovascular diseases; thrombosis; platelets; lymphocytes; endothelium
资金
- NHLBI NIH HHS [HL 47073, HL 46403] Funding Source: Medline
- NINDS NIH HHS [NS 41462] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL046403, R01HL047073, R37HL047073] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS041462] Funding Source: NIH RePORTER
Introduction: 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. Materials and methods: Lymphocytes were isolated from 46 patients with angio-graphically proven coronary artery disease (CAD) as well as from matched healthy control subjects. Ectonucleotidase ADPase and ATPase activities (prototypical for the ATPDase activity of endothetial cells) were measured using established radio-TLC procedures. Results and discussion: 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 platetet-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. (c) 2004 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据