Persistent Activation of Nuclear Factor Kappa-B Signaling Pathway in Patients With Unstable Angina and Elevated Levels of C-Reactive Protein
| Autor: | Giovanna Liuzzo, Annalisa Porto, Matteo Santamaria, Luigi M. Biasucci, Michela Pinnelli, Attilio Maseri, Valeria Colafrancesco, Vittoria Rizzello, Filippo Crea, Michela Narducci, Salvatore Brugaletta |
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| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
biology Lipopolysaccharide Unstable angina business.industry Monocyte C-reactive protein Interleukin medicine.disease Proinflammatory cytokine Angina chemistry.chemical_compound medicine.anatomical_structure Endocrinology chemistry Internal medicine Immunology medicine biology.protein Tumor necrosis factor alpha Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of the American College of Cardiology. 49:185-194 |
| ISSN: | 0735-1097 |
| DOI: | 10.1016/j.jacc.2006.07.071 |
| Popis: | Objectives Our study investigated: 1) the contribution of nuclear factor kappa-B (NF-κB) 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-κB activation. Background Unstable angina patients with elevated CRP have enhanced inflammatory response and increased risk of persistent instability, myocardial infarction, and death. Methods 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-κB activation and interleukin (IL)-6 and tumor necrosis factor (TNF)-α 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 μg/ml), lipopolysaccharide (LPS) (1 to 10 ng/ml), or both. Results Spontaneous NF-κB activation in vivo was demonstrated in 82% of group 1 versus 14% of group 2 and 21% of group 3 patients (p Conclusions 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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