Ritchie M E
Division of Cardiology and Cardiovascular Research Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Circulation. 1998 Oct 27;98(17):1707-13. doi: 10.1161/01.cir.98.17.1707.
Nuclear factor-kappaB (NF-kappaB) resides inactive in the cytoplasm of lymphocytes, monocytes, endothelial cells, and smooth muscle cells, where, after stimulation, it transcriptionally activates interleukins, interferon, tumor necrosis factor-alpha, and adhesion molecules. Because acute inflammation may play a role in coronary artery plaque rupture, it was hypothesized that NF-kappaB activation correlated with coronary artery disease (CAD) activity.
Evidence of NF-kappaB activation in the circulation of 102 consecutive patients without an acute myocardial infarction who were undergoing cardiac catheterization was determined. Of these, 19 had unstable angina (USA) and were within 24 hours of the last episode of chest pain. The remaining 83 were being evaluated for stable angina (53), valvular heart disease (8), atypical chest pain (12), or congestive heart failure (10). Evidence of NF-kappaB activation was determined by electromobility shift assays (EMSAs) with the NF-kappaB binding-site-specific probe and nuclear proteins isolated from the buffy coat of blood obtained at the beginning of the procedure. Specificity of this DNA-protein interaction was confirmed by competition and supershift EMSAs. Analyses showed that 17 of 19 patients with USA had marked activation of NF-kappaB. Despite a significant number of patients with severe CAD (69%), only 2 of the 83 without USA showed marked NF-kappaB activation. A lack of NF-kappaB activation was not due to a lack of functional cell/protein because NF-kappaB was appropriately activated by lipopolysaccharide ex vivo in all patients. NF-kappaB activation was not a nonspecific response of all transcription factors because neither Sp1 or Oct1 was activated in patients with activated NF-kappaB. There was no relationship between drugs used, hemodynamic status, or other clinical characteristics and state of NF-kappaB activation.
These data show that NF-kappaB is specifically and significantly activated in unstable angina pectoris and is not affected by severity of CAD or medical therapy. Furthermore, because NF-kappaB is activated before a clinical event, it may be mechanistically involved in the plaque disruption that produces acute coronary artery syndromes.
核因子-κB（NF-κB）以无活性状态存在于淋巴细胞、单核细胞、内皮细胞和平滑肌细胞的细胞质中，在受到刺激后，它会转录激活白细胞介素、干扰素、肿瘤坏死因子-α和黏附分子。由于急性炎症可能在冠状动脉斑块破裂中起作用，因此推测NF-κB激活与冠状动脉疾病（CAD）活动相关。
确定了102例连续接受心脏导管插入术且无急性心肌梗死患者循环中NF-κB激活的证据。其中，19例患有不稳定型心绞痛（USA），且处于最后一次胸痛发作的24小时内。其余83例正在接受稳定型心绞痛（53例）、心脏瓣膜病（8例）、非典型胸痛（12例）或充血性心力衰竭（10例）的评估。通过电泳迁移率变动分析（EMSA），使用NF-κB结合位点特异性探针和从手术开始时采集的血液中白细胞层分离的核蛋白，来确定NF-κB激活的证据。这种DNA-蛋白质相互作用的特异性通过竞争和超迁移EMSA得以证实。分析表明，19例USA患者中有17例NF-κB有明显激活。尽管有大量严重CAD患者（69%），但83例无USA的患者中只有2例显示出明显的NF-κB激活。缺乏NF-κB激活并非由于缺乏功能性细胞/蛋白质，因为在所有患者中，脂多糖在体外均能适当激活NF-κB。NF-κB激活并非所有转录因子的非特异性反应，因为在NF-κB激活的患者中，Sp1或Oct1均未被激活。所用药物、血流动力学状态或其他临床特征与NF-κB激活状态之间均无关联。
这些数据表明，NF-κB在不稳定型心绞痛中被特异性且显著激活，且不受CAD严重程度或药物治疗的影响。此外，由于NF-κB在临床事件发生前就被激活，它可能在导致急性冠状动脉综合征的斑块破裂过程中起机制性作用。
