Enhanced levels of soluble and membrane-bound CD40 ligand in patients with unstable angina -: Possible reflection of T lymphocyte and platelet involvement in the pathogenesis of acute coronary syndromes
Enhanced levels of soluble and membrane-bound CD40 ligand in patients with unstable angina -: Possible reflection of T lymphocyte and platelet involvement in the pathogenesis of acute coronary syndromes
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DOI：
10.1161/01.cir.100.6.614
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发表时间：
1999-08-10
期刊：
影响因子：
37.8
通讯作者：
Gullestad, L
中科院分区：
文献类型：
--
作者：
Aukrust, P;Müller, F;Gullestad, L
背景-活化T细胞和血小板上的CD 40配体（CD 40 L）可能激活基质金属蛋白酶，诱导促凝血活性，并通过促进动脉粥样硬化斑块破裂参与急性冠状动脉综合征的发病机制。我们分析了29名稳定型心绞痛患者、26名不稳定型心绞痛患者和19名对照者外周血中可溶性和膜结合CD 40 L的水平。我们的主要发现如下。(1)与稳定型心绞痛患者和对照组相比，不稳定型心绞痛患者血清sCD 40 L水平显著升高。(2)血小板可以释放大量的sCD 40 L时，刺激离体与凝血酶受体激动剂肽SFLLRN在患者和对照组。(3)不稳定型心绞痛患者血小板减少的特征是细胞内水平降低和SFLLRN刺激的sCD 40 L释放减少，这可能代表这些患者脱颗粒血小板的百分比较高。(4)与稳定型心绞痛患者和对照组相比，不稳定型心绞痛患者的T细胞表面CD 40 L表达增强，抗CD 3/抗CD 28刺激时sCD 40 L释放增加。(5)重组CD 40 L和来自具有高sCD 40 L水平的不稳定型心绞痛患者的血清诱导单核细胞释放单核细胞趋化肽-1（一种参与动脉粥样硬化发病机制的CC-趋化因子）的增强。表明CD 40 L-CD 40相互作用可能在长期动脉粥样硬化过程和急性冠状动脉综合征的触发和传播中起致病作用。
Background-The CD40 ligand (CD40L) on activated T cells and platelets may be activating matrix metalloproteinases, inducing procoagulant activity, and be involved in the pathogenesis of acute coronary syndromes by promoting plaque rupture in atheroma.Methods and Results-To study the role of CD40L-CD40 interaction in coronary disease, we analyzed levels of soluble (s) and membrane-bound CD40L in the peripheral blood from 29 patients with stable angina, 26 with unstable angina, and 19 controls. Our main findings follow. (1) Patients with unstable angina had significantly raised serum levels of sCD40L when compared with patients with stable angina and controls. (2) Platelets could release large amounts of sCD40L when stimulated ex vivo with the thrombin receptor-agonist peptide SFLLRN in both patients and controls. (3) Platelets in patients with unstable angina were characterized ex vivo by decreased intracellular levels and decreased SFLLRN-stimulated release of sCD40L, which may possibly represent a higher percentage of degranulated platelets in these patients. (4) T cells in patients with unstable angina had enhanced surface expression of CD40L and increased release of sCD40L on anti-CD3/anti-CD28 stimulation in vitro when compared with patients with stable angina and controls. (5) Recombinant CD40L and serum from patients with unstable angina who had high sCD40L levels induced enhanced release of monocyte chemoattractant peptide-1 from mononuclear cells, a CC-chemokine involved in the pathogenesis of atherosclerosis.Conclusions-This first demonstration of enhanced levels of soluble and membrane-bound forms of CD40L in angina patients, with particularly high levels in patients with unstable angina, suggests that CD40L-CD40 interaction may play a pathogenic role in both the long-term atherosclerotic process and in the triggering and propagation of acute coronary syndromes.