Redox biology of blood.

Antioxidants and Redox Signaling (Impact Factor: 7.67). 01/2005; 6(6):941-3. DOI: 10.1089/ars.2004.6.941
Source: PubMed
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    ABSTRACT: Prognosis of clinical outcome following myocardial infarction is variable and difficult to predict. We have analyzed the plasma proteome of thirty patients with acute myocardial infarction to search for new prognostic biomarkers. Proteomic analyses of blood samples were performed by 2-D-DiGE after plasma depletion of albumin and immunoglobulins G. New York Heart Association (NYHA) class determined at 1-year follow-up was used to identify patients with heart failure. Principal component analysis and hierarchical clustering of proteomic data revealed that patients could be separated into 3 groups. The 22 differentially expressed proteins involved in this grouping were identified as haptoglobin (Hp) and respective isoforms. The 3 groups of patients had distinct Hp isoforms: patients from group 1 had the α1-α1, patients from group 2 the α2-α1, and patients from group 3 the α2-α2 genotype. This classification was also associated with different total plasma levels of Hp. The presence of the α2 genotype and low plasma levels of Hp was associated with a higher NYHA class and therefore with a detrimental functional outcome after myocardial infarction. A plasma level of Hp below 1.4g/L predicted the occurrence of heart failure (NYHA 2, 3, 4) at 1-year with 100% sensitivity.
    Journal of proteomics 07/2011; 75(1):229-36. · 5.07 Impact Factor
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    ABSTRACT: Haptoglobin (Hpt) is known to capture circulating free hemoglobin (Hb) and bind apolipoprotein (Apo) A-I or E. Here, we report that Hb can be tightly bound by most of Hpt molecules (TB-Hpt, 80%), whereas loosely bound by a minor part of them (LB-Hpt, 20%). LB-Hpt amount was significantly increased (over 60%) in patients with acute coronary syndrome. LB-Hpt bound ApoA-I and ApoE less efficiently than TB-Hpt (8- and 4-fold less, respectively) and did not affect their activity of stimulating the enzyme lecithin-cholesterol acyltransferase. LB-Hpt and TB-Hpt displayed comparable levels of nitrotyrosine residues, but differences in glycan chains. Changes in LB-Hpt level might be associated with changes in Hpt functions.
    Biological Chemistry 02/2011; 392(4):371-6. · 2.69 Impact Factor
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    ABSTRACT: Apolipoprotein A-I (ApoA-I) is the main protein component of the high density lipoproteins and it plays an important role in the reverse cholesterol transport. In particular, it stimulates cholesterol efflux from peripheral cells toward liver and activates the enzyme lecithin-cholesterol acyltransferase (LCAT). Haptoglobin (Hpt), a plasma α(2) -glycoprotein belonging to the family of acute-phase proteins, binds to ApoA-I inhibiting the stimulation of the enzyme LCAT. Previously, we reported that a synthetic peptide, P2a, binds to and displaces Hpt from ApoA-I restoring the LCAT cholesterol esterification activity in the presence of Hpt. Here, we investigate the molecular determinants underlining the interaction between Hpt and P2a peptide. Analysis of truncated P2a analogs showed that P2a sequence can only be slight reduced in length at the N-terminal to preserve the ability of binding to Hpt. Binding assays showed that charged residues are not involved in Hpt recognition; actually, E146A and D157A substitutions increase the binding affinity to Hpt. Biological characterization of the corresponding P2a peptide analogs, Apo146 and Apo157, showed that the two peptides interfere with Hpt binding to HDL and are more effective than P2a peptide in rescue LCAT activity from Hpt inhibition. This result suggests novel hints to design peptides with anti-atherogenic activity. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.
    Journal of Peptide Science 02/2013; 19(4). · 1.86 Impact Factor