Yan Jin-chuan, Wu Zong-gui, Kong Xian-tao, Zong Ren-qian, Zhan Lin-zen
Department of Cardiology, Affiliated Zhong Da Hospital, Southeast University, Nanjing 210009, China.
Acta Pharmacol Sin. 2004 Feb;25(2):251-6.
To investigate whether upregulation of CD40-CD40 ligand system is related to matrix metalloproteinases level and stability of coronary atherosclerotic plaque in patients with acute coronary syndrome (ACS).
Sixteen normal controls and 56 patients including 24 with stable angina (SA), 20 with unstable angina (UA), and 12 with acute myocardial infarction (AMI) were investigated. The expression of CD40 and CD40L on platelet was analyzed by flow cytometry. Serum soluble CD40L (sCD40L), MMP-9 and MMP-3 level was determined by ELISA. All coronary stenosis with > or =30% diameter reduction were assessed by angiographic coronary stenosis morphology.
Patients with ACS showed a significant increase of CD40 (75 +/- 12 MIF) and CD40L (13 +/- 4 MIF) coexpression on platelets compared with control and SA group (P<0.01). sCD40L also showed higher level in patients with ACS (10.2 +/- 3.5 microg/L) than in control (3.1 +/- 1.4 microg/L, P<0.01) and SA group (3.3 +/- 1.6 microg/L, P<0.01). Serum MMP-3 and MMP-9 in patients with ACS were two times greater than those in control. A positive correlation was found between MMP-9, MMP-3, and CD40L expression on platelets as well as sCD40L levels, but not for CD40 expression on platelets. An obvious correlation was also observed between sCD40L concentration and complex coronary stenoses (r=0.60, P<0.01).
Patients with ACS show increased coexpression of CD40 system, especially expression of CD40L, which may create a proinflammatory and prothrombotic milieu for aggravating the development of atherosclerosis and instability of atherosclerotic plaques, and may be a valuable marker for predicting the severity of ACS.
探讨急性冠状动脉综合征（ACS）患者CD40-CD40配体系统上调是否与基质金属蛋白酶水平及冠状动脉粥样硬化斑块稳定性相关。
对16名正常对照者和56例患者进行研究，其中包括24例稳定型心绞痛（SA）患者、20例不稳定型心绞痛（UA）患者和12例急性心肌梗死（AMI）患者。采用流式细胞术分析血小板上CD40和CD40L的表达。通过酶联免疫吸附测定法（ELISA）测定血清可溶性CD40L（sCD40L）、基质金属蛋白酶-9（MMP-9）和基质金属蛋白酶-3（MMP-3）水平。所有直径狭窄≥30%的冠状动脉狭窄均通过血管造影冠状动脉狭窄形态进行评估。
与对照组和SA组相比，ACS患者血小板上CD40（75±12平均荧光强度）和CD40L（13±4平均荧光强度）的共表达显著增加（P<0.01）。ACS患者的sCD40L水平（10.2±3.5μg/L）也高于对照组（3.1±1.4μg/L，P<0.01）和SA组（3.3±1.6μg/L，P<0.01）。ACS患者血清MMP-3和MMP-9水平是对照组的两倍。发现MMP-9、MMP-3与血小板上CD40L表达以及sCD40L水平之间呈正相关，但与血小板上CD40表达无关。sCD40L浓度与复杂冠状动脉狭窄之间也存在明显相关性（r=0.60，P<0.01）。
ACS患者CD40系统共表达增加，尤其是CD40L的表达，这可能营造一种促炎和促血栓形成的环境，加剧动脉粥样硬化的发展和动脉粥样硬化斑块的不稳定性，可能是预测ACS严重程度的一个有价值的标志物。
