Document Type
Article
Publication Date
11-13-2012
Publication Title
Circulation
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.
Repository Citation
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.; and Ischiropoulos, Harry, "Immunoglobulins Against Tyrosine-Nitrated Epitopes in Coronary Artery Disease" (2012). Mathematics and Statistics Faculty Publications. 201.
https://engagedscholarship.csuohio.edu/scimath_facpub/201
DOI
10.1161/CIRCULATIONAHA.112.103796
Version
Postprint
Volume
126
Issue
20
Comments
This work was supported by grants from the National Institutes of Health HL54926, HL103918, and ES013508; the National Institute of Environmental Health Sciences Center of Excellence in Environmental Toxicology to Dr Ischiropoulos; P01HL098055 and P01HL076491 to Dr Hazen; and R01HL103931 and 1P20HL113452 to Dr Tang.