Napoleão Patrícia, Santos M Cristina, Selas Mafalda, Viegas-Crespo Ana M, Pinheiro Teresa, Ferreira R Cruz
Centro de Biologia Ambiental, Universidade Lisboa, Lisboa, Portugal.
Rev Port Cardiol. 2007 Dec;26(12):1357-63.
Inflammation is now considered a key component of atherosclerosis, from fatty streak formation to plaque rupture, subsequent thrombosis, and progressive mechanical and dynamic obstruction. Rupture of the arterial plaque's fibrous cap exposes tissue factors present in the necrotic core, triggering inflammatory signaling, cell adhesion, and the coagulation cascade that eventually leads to thrombus. Cytokines and adhesion molecules are key components of these events that contribute to the development of an atherosclerotic plaque. The cytokine TNF-alpha and intercellular adhesion molecule-1 (ICAM-1) are indicators of basal inflammation, while the soluble forms of adhesion molecules such as CD40L and P-selectin indicate the extent of platelet activation. This study reports on the follow-up of 17 patients with confirmed acute myocardial infarction (AMI group) undergoing angioplasty and a matched control group of 16 patients without coronary artery disease as verified by coronary angiography. Patients from the AMI group were assessed at the onset of the acute coronary syndrome, within 24 h, before the administration of glycoprotein IIb/IIIa inhibitors and coronary angioplasty, and during the recovery period, two and 40 days after intervention. For both groups, clinical characteristics were documented and serum concentrations of soluble CD40L, P-selectin, ICAM-1, TNF-alpha, and conventional biochemical indicators were analyzed. For AMI patients, these indicators were recorded at study entry and during follow-up. Concentrations of cytokines and adhesion molecules were measured using commercial immunoassay (ELISA) kits. Significant variations in sP-selectin were observed relative to the control group. Immediately after myocardial infarction, sP-selectin levels rose markedly, followed by a sharp decrease two days later. After 40 days of recovery, sP-selectin levels rose again, returning to the initial values. Variations in sCD40L levels were not significant relative to controls. However, sCD40L concentrations tended to fall until the second day after infarction, followed by a rise, and by the 40th day of recovery levels were slightly higher than controls. Unlike sCD40L and sP-selectin, consistently higher levels of TNF-alpha relative to controls were observed, which were only significant after 40 days of recovery. No significant variations were observed for ICAM-1 serum concentrations in the AMI group. The variations observed demonstrate the role of inflammatory markers in AMI progression and highlight the importance of systemic inflammation in disease evolution. The increased concentration of sP-selectin at infarction onset is evidence of thrombosis and platelet activation. Later, during the recovery period when hemodynamic variables are returning to stability in part due to medication, rises in circulating levels of sCD40L and cytokines such as TNF-alpha may reflect the role of these molecules in the recovery of endothelial and myocardial tissues.
从脂肪条纹形成到斑块破裂、随后的血栓形成以及渐进性的机械和动态阻塞，炎症现在被认为是动脉粥样硬化的关键组成部分。动脉斑块纤维帽的破裂暴露了坏死核心中存在的组织因子，触发炎症信号传导、细胞粘附和凝血级联反应，最终导致血栓形成。细胞因子和粘附分子是这些事件的关键组成部分，它们促成了动脉粥样硬化斑块的发展。细胞因子肿瘤坏死因子-α（TNF-α）和细胞间粘附分子-1（ICAM-1）是基础炎症指标，而可溶性粘附分子如CD40L和P-选择素的形式则表明血小板活化的程度。本研究报告了17例确诊为急性心肌梗死患者（AMI组）接受血管成形术的随访情况，以及16例经冠状动脉造影证实无冠状动脉疾病的匹配对照组。AMI组患者在急性冠状动脉综合征发作时、24小时内、给予糖蛋白IIb/IIIa抑制剂和冠状动脉成形术前以及恢复期（干预后2天和40天）进行评估。对两组患者记录临床特征，并分析可溶性CD40L、P-选择素、ICAM-1、TNF-α的血清浓度以及传统生化指标。对于AMI患者，在研究入组时和随访期间记录这些指标。使用商业免疫测定（ELISA）试剂盒测量细胞因子和粘附分子的浓度。观察到相对于对照组，sP-选择素存在显著差异。心肌梗死后立即，sP-选择素水平显著升高，随后在两天后急剧下降。恢复40天后，sP-选择素水平再次升高，恢复到初始值。相对于对照组，sCD40L水平的差异不显著。然而，sCD40L浓度在梗死后天数趋于下降，直到第二天，随后上升，到恢复第40天时水平略高于对照组。与sCD40L和sP-选择素不同，观察到相对于对照组，TNF-α水平持续较高，仅在恢复40天后显著。AMI组ICAM-1血清浓度未观察到显著差异。观察到的这些变化证明了炎症标志物在AMI进展中的作用，并突出了全身炎症在疾病演变中的重要性。梗死发作时sP-选择素浓度升高是血栓形成和血小板活化的证据。后来，在恢复期，由于药物治疗，血流动力学变量部分恢复稳定，sCD40L和细胞因子如TNF-α循环水平的升高可能反映了这些分子在内皮和心肌组织恢复中的作用。
