Immunoglobulins against tyrosine-nitrated epitopes in coronary artery disease

Leonor Thomson, Margarita Tenopoulou, Richard Lightfoot, Epida Tsika, Ioannis Parastatidis, Marissa Martinez, Todd M. Greco, Paschalis Thomas Doulias, Yuping Wu, W. H.Wilson Tang, Stanley L. Hazen, Harry Ischiropoulos

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

BACKGROUND-: Several lines of evidence support a pathophysiological role of immunity in atherosclerosis. Tyrosine-nitrated proteins, a footprint of oxygen- and nitrogen-derived oxidants generated by cells of the immune system, are enriched in atheromatous lesions and in circulation of patients with coronary artery disease (CAD). However, the consequences of possible immune reactions triggered by the presence of nitrated proteins in subjects with clinically documented atherosclerosis have not been explored. METHODS AND RESULTS-: Specific immunoglobulins that recognize 3-nitrotyrosine epitopes were identified in human lesions, as well as in circulation of patients with CAD. The levels of circulating immunoglobulins against 3-nitrotyrosine epitopes were quantified in patients with CAD (n=374) and subjects without CAD (non-CAD controls, n=313). A 10-fold increase in the mean level of circulating immunoglobulins against protein-bound 3-nitrotyrosine was documented in patients with CAD (3.75±1.8 μg antibody Eq/mL plasma versus 0.36±0.8 μg antibody Eq/mL plasma), and was strongly associated with angiographic evidence of significant CAD. CONCLUSIONS-: The results of this cross-sectional study suggest that posttranslational modification of proteins via nitration within atherosclerotic plaque-laden arteries and in circulation serve as neo-epitopes for the elaboration of immunoglobulins, thereby providing an association between oxidant production and the activation of the immune system in CAD.

Original languageEnglish (US)
Pages (from-to)2392-2401
Number of pages10
JournalCirculation
Volume126
Issue number20
DOIs
StatePublished - Nov 13 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Keywords

  • antibodies
  • antigens
  • atherosclerosis
  • free radicals
  • immune system
  • nitric oxide

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