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Enhanced levels of CD154 (CD40 ligand) on platelets in patients with chronic heart failure
Author(s) -
Stumpf Christian,
Lehner Christoph,
Eskafi Saeed,
Raaz Dorette,
Yilmaz Atilla,
Ropers Susanne,
Schmeisser Alexander,
Ludwig Joseph,
Daniel Werner G.,
Garlichs Christoph D.
Publication year - 2003
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/s1388-9842(03)00110-7
Subject(s) - medicine , proinflammatory cytokine , heart failure , platelet activation , ejection fraction , cd154 , cardiology , inflammation , platelet , endothelial activation , cd40 , in vitro , biochemistry , chemistry , cytotoxic t cell
Background: Inflammation plays a significant contributory role in the pathogenesis of chronic heart failure (CHF). Previous data have shown enhanced plasma levels of proinflammatory cytokines, i.e. TNF‐α and IL‐6, as well as a persistent immune activation in patients with CHF. Furthermore, the immune modulator CD154 has been receiving increased attention, since it plays a key role in the pathophysiology of multicellular vascular events such as thrombosis, inflammation and atherosclerosis. Since CD154 intitiates and maintains the release of proinflammatory cytokines from endothelial cells, its potential role for the development and progression of CHF is of interest. Methods: Fifty patients with CHF (aged 66.9±12.6 years, mean ejection fraction 22.1±9.2%, NYHA II–IV, 39 of ischemic origin, 11 with idiopathic dilated cardiomyopathy) and 15 healthy controls (aged 62.5±9.8 years) were examined. Thirty‐two patients were taking aspirin (100 mg/day). Blood was drawn from a peripheral vein and immediately fixed with 1% paraformaldehyde, incubated with anti‐CD154, anti‐P‐selectin, and anti‐CD61 and thereafter analyzed by flow cytometry. Results: Patients with CHF showed significantly enhanced expression of platelet‐bound CD154 and P‐selectin as compared to controls (CD154: median 35.6 25th percentile: 26.3; 75th percentile: 44.6 vs. 12.8; 25th: 6.8; 75th: 15.6 mean fluorescence intensity [MFI], P <0.001; P‐selectin: median 3.2 25th percentile: 1.9; 75th percentile: 5.9 vs. 1.4; 25th: 1.2; 75th: 1.9, MFI, P <0.001). CD154 expression on platelets positively correlated with increasing NYHA‐class. In contrast, no significant differences in serum levels of soluble CD154 or CD40 expression on monocytes were detected in the study groups. Antiplatelet‐therapy with aspirin did not influence CD154 or P‐selectin expression on platelets. Conclusion: Our pilot study demonstrates significantly enhanced levels of CD154 on platelets in patients with CHF. This suggests that the CD40–CD154 axis may contribute to the proinflammatory milieu, which exists in CHF and thus may play a pathogenic role in the development and progression of CHF.