TY - JOUR
T1 - Immunoglobulins against tyrosine-nitrated epitopes in coronary artery disease
AU - Thomson, Leonor
AU - Tenopoulou, Margarita
AU - Lightfoot, Richard
AU - Tsika, Epida
AU - Parastatidis, Ioannis
AU - Martinez, Marissa
AU - Greco, Todd M.
AU - Doulias, Paschalis Thomas
AU - Wu, Yuping
AU - Tang, W. H.Wilson
AU - Hazen, Stanley L.
AU - Ischiropoulos, Harry
PY - 2012/11/13
Y1 - 2012/11/13
N2 - 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.
AB - 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.
KW - antibodies
KW - antigens
KW - atherosclerosis
KW - free radicals
KW - immune system
KW - nitric oxide
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U2 - 10.1161/CIRCULATIONAHA.112.103796
DO - 10.1161/CIRCULATIONAHA.112.103796
M3 - Article
C2 - 23081989
AN - SCOPUS:84869231009
SN - 0009-7322
VL - 126
SP - 2392
EP - 2401
JO - Circulation
JF - Circulation
IS - 20
ER -