Immunoglobulins Against Tyrosine-Nitrated Epitopes in Coronary Artery Disease

• Published in: Circulation (New York, N.Y.) Vol. 126; no. 20; pp. 2392 - 2401
• Main Authors: Thomson, Leonor, Tenopoulou, Margarita, Lightfoot, Richard, Tsika, Epida, Parastatidis, Ioannis, Martinez, Marissa, Greco, Todd M., Doulias, Paschalis-Thomas, Wu, Yuping, Tang, W.H. Wilson, Hazen, Stanley L., Ischiropoulos, Harry
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 13.11.2012
• Subjects: Aged; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Case-Control Studies; Coronary Angiography; Coronary Artery Disease - blood; Coronary Artery Disease - diagnostic imaging; Coronary Artery Disease - immunology; Coronary heart disease; Cross-Sectional Studies; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Epitopes - immunology; Female; Heart; Humans; Immune System - physiopathology; Immunoglobulins - blood; Male; Medical sciences; Middle Aged; Tyrosine - analogs & derivatives; Tyrosine - immunology; Tyrosine; Immunoglobulins; free radicals; Antigenic determinant; Cardiovascular disease; antigens; Coronary heart disease; Free radical; Vascular disease; Aminoacid; Nitric oxide; Atherosclerosis; antibodies; Immune system
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.112.103796

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. 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. 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.