Persistent activation of nuclear factor kappa-B signaling pathway in patients with unstable angina and elevated levels of C-reactive protein evidence for a direct proinflammatory effect of azide and lipopolysaccharide-free C-reactive protein on human monocytes via nuclear factor kappa-B activation
| Autor: | Giovanna, Liuzzo, Matteo, Santamaria, Luigi M, Biasucci, Michela, Narducci, Valeria, Colafrancesco, Annalisa, Porto, Salvatore, Brugaletta, Michela, Pinnelli, Vittoria, Rizzello, Attilio, Maseri, Filippo, Crea |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Lipopolysaccharides Male Azides Microscopy Confocal Interleukin-6 Tumor Necrosis Factor-alpha NF-kappa B Enzyme-Linked Immunosorbent Assay In Vitro Techniques Middle Aged Sensitivity and Specificity Monocytes C-Reactive Protein Reference Values Humans Female Angina Unstable Inflammation Mediators Aged Signal Transduction |
| Zdroj: | Journal of the American College of Cardiology. 49(2) |
| ISSN: | 1558-3597 |
| Popis: | 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 (p0.001). Interleukin-6 and TNF-alpha production was significantly correlated with the NF-kappaB activation status (r = 0.55, p0.001 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 (p0.01 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. |
| Databáze: | OpenAIRE |
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