Gidron Yori, Gilutz Harel, Berger Rivka, Huleihel Mahmoud
Department of Sociology of Health, Faculty of Health Sciences, Ben-Gurion University, Be'er Sheeba, Israel.
Cardiovasc Res. 2002 Oct;56(1):15-21. doi: 10.1016/s0008-6363(02)00537-0.
This review article integrates empirical findings from various scientific disciplines into a proposed psychoneuroimmunological (PNI) model of the acute coronary syndrome (ACS). Our starting point is an existing, mild, atherosclerotic plaque and a dysfunctional endothelium. The ACS is triggered by three stages. (1) Plaque instability: Pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha) and chemoattractants (MCP-1, IL-8) induce leukocyte chemoattraction to the endothelium, and together with other triggers such as the CD40L-CD40 co-stimulation system activate plaque monocytes (macrophages). The macrophages then produce matrix metalloproteinases that disintegrate extra-cellular plaque matrix, causing coronary plaque instability. Acute stress, hostility, depression and vital exhaustion (VE) have been associated with elevated pro-inflammatory cytokines and leukocyte levels and their recruitment. (2) Extra-plaque factors promoting rupture: Neuro-endocrinological factors (norepinephrine) and cytokines induce vasoconstriction and elevated blood pressure (BP), both provoking a vulnerable plaque to rupture. Hostility/anger and acute stress can lead to vasoconstriction and elevated BP via catecholamines. (3) Superimposed thrombosis at a ruptured site: Increases in coagulation factors and reductions in anticoagulation factors (e.g. protein C) induced by inflammatory factors enhance platelet aggregation, a key stage in thrombosis. Hostility, depression and VE have been positively correlated with platelet aggregation. Thrombosis can lead to severe coronary occlusion, clinically manifested as an ACS. Thus, PNI processes might, at least in part, contribute to the pathogenesis of the ACS. This chain of events may endure due to lack of neuroendocrine-to-immune negative feedback stemming from cortisol resistance. This model has implications for the use of psychological interventions in ACS patients.
这篇综述文章将来自不同科学学科的实证研究结果整合到一个急性冠状动脉综合征（ACS）的心理神经免疫学（PNI）模型中。我们的出发点是一个现有的轻度动脉粥样硬化斑块和功能失调的内皮。ACS由三个阶段触发。（1）斑块不稳定：促炎细胞因子（IL-1、IL-6、肿瘤坏死因子-α）和趋化因子（单核细胞趋化蛋白-1、IL-8）诱导白细胞向内皮趋化，并与其他触发因素（如CD40L-CD40共刺激系统）一起激活斑块单核细胞（巨噬细胞）。然后巨噬细胞产生基质金属蛋白酶，分解细胞外斑块基质，导致冠状动脉斑块不稳定。急性应激、敌意、抑郁和心力交瘁（VE）与促炎细胞因子和白细胞水平升高及其募集有关。（2）促进破裂的斑块外因素：神经内分泌因素（去甲肾上腺素）和细胞因子诱导血管收缩和血压（BP）升高，两者都促使易损斑块破裂。敌意/愤怒和急性应激可通过儿茶酚胺导致血管收缩和血压升高。（3）破裂部位的叠加血栓形成：炎症因子诱导的凝血因子增加和抗凝因子（如蛋白C）减少增强血小板聚集，这是血栓形成的关键阶段。敌意、抑郁和VE与血小板聚集呈正相关。血栓形成可导致严重的冠状动脉阻塞，临床表现为ACS。因此，PNI过程可能至少部分促成ACS的发病机制。由于缺乏源于皮质醇抵抗的神经内分泌对免疫的负反馈，这一系列事件可能会持续。该模型对ACS患者心理干预的应用具有启示意义。
