Liuzzo Giovanna, Santamaria Matteo, Biasucci Luigi M, Narducci Michela, Colafrancesco Valeria, Porto Annalisa, Brugaletta Salvatore, Pinnelli Michela, Rizzello Vittoria, Maseri Attilio, Crea Filippo
Institute of Cardiology, Catholic University, Rome, Italy.
J Am Coll Cardiol. 2007 Jan 16;49(2):185-94. doi: 10.1016/j.jacc.2006.07.071. Epub 2006 Dec 29.
Our study investigated: 1) the contribution of nuclear factor kappa-B (NF-kappaB) signaling pathway to the enhanced inflammatory response observed in unstable angina (UA) patients with elevated levels of C-reactive protein (CRP); and 2) whether CRP may have direct proinflammatory effects via NF-kappaB activation.
Unstable angina patients with elevated CRP have enhanced inflammatory response and increased risk of persistent instability, myocardial infarction, and death.
We studied 28 patients with history of UA and persistently elevated CRP (>3 mg/l) followed for 24 months and free of symptoms for at least 6 months (group 1), 14 patients with history of UA and low CRP (group 2), and 24 patients with chronic stable angina and low CRP (group 3). Peripheral blood monocytes were analyzed for spontaneous NF-kappaB activation and interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha production. To assess the direct proinflammatory effects of CRP, monocytes from 8 healthy subjects were stimulated in vitro with increasing doses of CRP (5 to 10 to 25 microg/ml), lipopolysaccharide (LPS) (1 to 10 ng/ml), or both.
Spontaneous NF-kappaB activation in vivo was demonstrated in 82% of group 1 versus 14% of group 2 and 21% of group 3 patients (p < 0.001). Interleukin-6 and TNF-alpha production was significantly correlated with the NF-kappaB activation status (r = 0.55, p < 0.001 and r = 0.53, p = 0.006, respectively). Patients with NF-kappaB activation had recurrence of acute coronary events (60% vs. 28%; p = 0.017). C-reactive protein induced a significant but modest in vitro NF-kappaB activation in human monocytes (p = 0.002). Coincubation with LPS produced a greater-than-additive response (p < 0.01 vs. CRP and LPS alone).
Nuclear factor kappa-B activation might represent a mechanism by which CRP amplifies and perpetuates the inflammatory component of acute coronary syndromes and influences the clinical outcome.
我们的研究调查了：1）核因子κB（NF-κB）信号通路对C反应蛋白（CRP）水平升高的不稳定型心绞痛（UA）患者中观察到的炎症反应增强的作用；以及2）CRP是否可能通过NF-κB激活产生直接的促炎作用。
CRP升高的不稳定型心绞痛患者炎症反应增强，持续不稳定、心肌梗死和死亡风险增加。
我们研究了28例有UA病史且CRP持续升高（>3mg/l）并随访24个月且至少6个月无症状的患者（第1组），14例有UA病史且CRP水平低的患者（第2组），以及24例慢性稳定型心绞痛且CRP水平低的患者（第3组）。分析外周血单核细胞的自发NF-κB激活以及白细胞介素（IL）-6和肿瘤坏死因子（TNF）-α的产生。为了评估CRP的直接促炎作用，用递增剂量的CRP（5至10至25μg/ml）、脂多糖（LPS）（1至10ng/ml）或两者在体外刺激8名健康受试者的单核细胞。
第1组82%的患者体内存在自发NF-κB激活，而第2组为14%，第3组为21%（p<0.001）。白细胞介素-6和TNF-α的产生与NF-κB激活状态显著相关（r=0.55，p<...
