Oxidized proteins in plasma of patients with heart failure: Role in endothelial damage

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 immumoglobulin 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, alpha-1-antitrypsin and fibrinogen, which underwent oxidation. Oxidation of alpha-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 alpha-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. (C) 2008 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.