Impaired platelet production of nitric oxide predicts presence of acute coronary syndromes
Impaired platelet production of nitric oxide predicts presence of acute coronary syndromes
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DOI：
10.1161/01.cir.98.15.1481
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发表时间：
1998-10-13
期刊：
影响因子：
37.8
通讯作者：
Vita, JA
中科院分区：
文献类型：
--
作者：
Freedman, JE;Ting, B;Vita, JA
背景-冠状动脉血管内血栓形成是大多数急性冠状动脉综合征的急性诱因.最近，已在人血小板中鉴定出组成型一氧化氮合酶（cNOS），并且已显示血小板衍生的一氧化氮抑制血小板聚集后的募集。然而，它在调节血小板反应在正常或病理条件下的作用还没有阐明。方法和结果-我们研究了一氧化氮（NO）的生产从87例患者进行冠状动脉造影，37稳定型心绞痛和50不稳定型心绞痛或心肌梗死2周内分离的血小板。用5 μ mol/LADP刺激后，用适用于标准血小板聚集仪的NO选择性微电极同时测量血小板聚集和NO产生。稳定型心绞痛和急性冠状动脉综合征患者的平均（+/- SEM）血小板源性NO生成量分别为1.78 +/- 0.36 pmol/10（8）和0.26 +/- 0.05 pmol/10（8）血小板（P = 0.0001）。通过逻辑回归分析，肝素治疗（比值比6.6，CI 1.9 - 22.8，P = 0.003）、血小板-NO生成降低（比值比4.0，CI 1.3 - 11.5，P = 0.01）和动脉粥样硬化程度（比值比1.5，CI 1.1 - 2.0，P = 0.02）是急性冠状动脉综合征的独立预测因子。在有动脉粥样硬化血管造影证据的患者亚组（n = 83）中，logistic回归显示血小板NO生成（比值比3.9，CI 1.3至11.1，P = 0.01）和肝素治疗（比值比6.3，CI 1.9至22.0，P = 0.004）是急性冠状动脉综合征的独立预测因素，而动脉粥样硬化的程度则没有。结论-总之，急性冠状动脉综合征患者聚集的血小板产生较少的NO。由于血小板聚集和血栓形成与不稳定型心绞痛和心肌梗死有关，受损的血小板衍生的NO产生可能有助于急性冠状动脉综合征的发展。
Background - Thrombus formation within a coronary vessel is the acute precipitating event in most acute coronary syndromes. Recently, constitutive nitric oxide synthase (cNOS) has been identified in human platelets, and platelet-derived nitric oxide has been shown to inhibit platelet recruitment after aggregation. However, its role in regulating platelet responses under normal or pathologic conditions has not yet been elucidated.Methods and Results - We examined nitric oxide (NO) production by platelets isolated from 87 patients undergoing coronary angiography, 37 with stable angina and 50 with unstable angina or a myocardial infarction within 2 weeks. After stimulation with 5 mu mol/L ADP, platelet aggregation and NO production were simultaneously measured with an NO-selective microelectrode adapted for use in a standard platelet aggregometer. Mean (+/- SEM) platelet-derived NO production was 1.78 +/- 0.36 pmol/10(8) and 0.26 +/- 0.05 pmol/10(8) platelets in coronary patients with stable angina and acute coronary syndromes, respectively (P = 0.0001). By logistic regression analysis, heparin treatment (odds ratio 6.6, CI 1.9 to 22.8, P = 0.003), lower platelet-NO production (odds ratio 4.0, CI 1.3 to 11.5, P = 0.01), and extent of atherosclerosis (odds ratio 1.5, CI 1.1 to 2.0, P = 0.02) were independent predictors of an acute coronary syndrome. In the subset of patients with angiographic evidence of atherosclerosis (n = 83), logistic regression demonstrated that platelet NO production (odds ratio 3.9, CI 1.3 to 11.1, P = 0.01) and heparin treatment (odds ratio 6.3, CI 1.9 to 22.0, P = 0.004) were independent predictors of an acute coronary syndrome, whereas extent of atherosclerosis was not.Conclusions - In summary, aggregating platelets from patients with acute coronary syndromes produce less NO. Since platelet aggregation and thrombus formation are implicated in unstable angina and myocardial infarction, impaired platelet-derived NO production may contribute to the development of acute coronary syndromes.