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).


OBJECTIVE
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, 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.
Banfi
Cristina
C
Monzino Cardiologic Center, IRCCS, Milan, Italy.
Brioschi
Maura
M
Barcella
Simona
S
Veglia
Fabrizio
F
Biglioli
Paolo
P
Tremoli
Elena
E
Agostoni
PierGiuseppe
P
D000368:Aged; D002470:Cell Survival; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006333:Heart Failure / Q000097:blood* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D040901:Proteomics; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin; D005340:Fibrinogen