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

Abstract

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 b 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.

Peroxisome Proliferator-Activated Receptor α Agonism Prevents Renal Damage and the Oxidative Stress and Inflammatory Processes Affecting the Brains of Stroke-Prone Rats

“…In addition, their chemical stability makes them suitable for laboratory measurement (Griffiths, 2000). The detection of high levels of protein carbonyls is a sign of oxidative stress and protein dysfunction (Dalle-Donne et al, 2003;Banfi et al, 2008), but we cannot exclude the possibility that other types of oxidative modification occur in salt-loaded and vehicle-treated SHRSPs.…”

“…Protein carbonyls were measured in the plasma samples and brain homogenates of animals sacrificed after 6 weeks of dietary treatment (Banfi et al, 2008) by using a Zentech PC test ELISA in accordance with the manufacturer's instructions (Biocell, Papatoetoe, Auckland, New Zealand). The plasma was collected in a citrate solution (0.129 M) and prepared by centrifugation at 1500g for 10 min at 4°C.…”

Acute Phase Proteins: Structure and Function Relationship

“…It is now recognized that oxidation of proteins plays an essential role in the pathogenesis of an important number of degenerative diseases. Compared to controls more oxidized proteins are found in tissues from animals and patients suffering from Alzheimer's disease, rheumatoid arthritis, atherosclerosis or amyotrophic lateral sclerosis (Banfi et al, 2008). For example, in plasma from patients with Alzheimer`s disease the most obviously oxidized proteins were identified as isoforms of AAT and fibrinogen -chain precursor proteins.…”

Polymerization and Oxidation of Alpha-1-Antitrypsin in Pathogenesis of Emphysema

“…They also found that oxyA1AT might be an independent predictor of protein-energy wasting in patients on hemodialysis. Oxidized A1AT was also detected in patients with Alzheimer's disease, heart failure, and in premature rupture of the fetal membrane (Choi et al, 2002;Banfi et al, 2008;Izumi-Yoneda et al, 2009). …”