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Oxidized proteins in plasma of patients with heart failure: Role in endothelial damage
Author(s) -
Banfi Cristina,
Brioschi Maura,
Barcella Simona,
Veglia Fabrizio,
Biglioli Paolo,
Tremoli Elena,
Agostoni PierGiuseppe
Publication year - 2008
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/j.ejheart.2008.01.016
Subject(s) - fibrinogen , blood proteins , oxidative stress , heart failure , medicine , albumin , pathogenesis , in vitro , endothelial dysfunction , antibody , biochemistry , endocrinology , chemistry , immunology
Background: Oxidative stress is increased in the failing heart, and this might contribute to the pathogenesis of myocardial remodelling and heart failure (HF). Aim: To identify the oxidized proteins in plasma of chronic HF patients and to evaluate their possible role in endothelial damage. Methods: Plasma levels of oxidized proteins were measured by immunoassay and by analysis in albumin and immunoglobulin depleted plasma using a proteomic approach, in 40 HF patients and in 20 age‐matched normal subjects. Analysis of the effects of proteins oxidized in vitro on human endothelial cell (EC) viability was also performed. Results: Plasma levels of oxidized proteins were significantly higher in HF patients than in controls ( p < 0.01). We identified two proteins, α‐1‐antitrypsin and fibrinogen, which underwent oxidation. Oxidation of α‐1‐antitrypsin resulted in loss of its protease inhibitor activity, thus leading to EC death in the presence of elastase. Fibrinogen, when oxidized, became otherwise cytotoxic and induced apoptosis in EC. Conclusions: This study shows that plasma levels of oxidized proteins are increased in HF, and permitted the identification of two proteins, namely α‐1‐antitrypsin and fibrinogen, which underwent oxidation. In vitro results highlighted the potential role of oxidized proteins in the EC damage that occurs in HF.