en
Scientific article
English

Treatment with recombinant tissue plasminogen activator (r-TPA) induces neutrophil degranulation in vitro via defined pathways

Published inVascular pharmacology, vol. 64, no. 41, p. 16-27
Publication date2015
Abstract

Autoantibodies to apolipoprotein A-I (anti-apoA-I IgG) have been shown to be both markers and mediators of cardiovascular disease, promoting atherogenesis and unstable atherosclerotic plaque. Previous studies have shown that high levels of anti-apoA-I IgGs are independently associated with major adverse cardiovascular events in patients with myocardial infarction. Autoantibody responses to apoA-I can be polyclonal and it is likely that more than one epitope may exist. To identify the specific immunoreactive peptides in apoA-I, we have developed a set of methodologies and procedures to isolate, purify, and identify novel apoA-I endogenous epitopes. First, we generated high purity apoA-I from human plasma, using thiophilic interaction chromatography followed by enzymatic digestion specifically at lysine or arginine residues. Immunoreactivity to the different peptides generated was tested by ELISA using serum obtained from patients with acute myocardial infarction and high titers of autoantibodies to native apoA-I. The immunoreactive peptides were further sequenced by mass spectrometry. Our approach successfully identified two novel immunoreactive peptides, recognized by autoantibodies from patients suffering from myocardial infarction, who contain a high titer of anti-apoA-I IgG. The discovery of these epitopes may open innovative prognostic and therapeutic opportunities potentially suitable to improve current cardiovascular risk stratification.

Keywords
  • Amino Acid Sequence
  • Apolipoprotein A-I/chemistry/immunology
  • Atherosclerosis/immunology
  • Autoantibodies/biosynthesis/blood
  • Biological Markers/analysis
  • Chromatography, Affinity
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes/chemistry/immunology
  • Gene Expression
  • Humans
  • Immunoglobulin G/biosynthesis/blood
  • Molecular Sequence Data
  • Myocardial Infarction/blood/diagnosis/immunology/pathology
  • Peptides/chemistry/immunology
  • Plaque, Atherosclerotic/blood/diagnosis/immunology/pathology
  • Sequence Analysis, Protein
Citation (ISO format)
CARBONE, Federico et al. Treatment with recombinant tissue plasminogen activator (r-TPA) induces neutrophil degranulation in vitro via defined pathways. In: Vascular pharmacology, 2015, vol. 64, n° 41, p. 16–27. doi: 10.1016/j.vph.2014.11.007
Main files (1)
Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal1537-1891
720views
4downloads

Technical informations

Creation02/16/2015 3:33:00 PM
First validation02/16/2015 3:33:00 PM
Update time03/14/2023 10:51:07 PM
Status update03/14/2023 10:51:06 PM
Last indexation01/16/2024 4:48:08 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack