Immunological detection of N omega-(Carboxymethyl)arginine by a specific antibody

N omega-(carboxymethyl)arginine (CMA) is an acid-labile advanced glycation end product (AGE) that was discovered in enzymatic hydrolysate of glycated collagen. Subsequently, CMA was also detected in human serum, and its level in patients with diabetes was found to be higher than in people without the disease. However, the histological localization of CMA and its pathophysiological significance remains poorly understood. Here, to address this issue, we developed a monoclonal antibody specific for CMA. This antibody reacted with CMA and CMA-protein adduct, whereas it did not cross-react with its analogues, such as N epsilon-(carboxymethyl)lysine and S-(carboxymethyl)cysteine, indicating that the antibody specifically recognizes CMA. Upon immunohistochemical analysis, a significant CMA immnoreactivity was found in atherosclerotic lesions, whereas no such immunoreactivity was observed in normal regions. This suggests that the accumulation of CMA in tissue proteins may contribute to the pathophysiologies associated with aging and age-related diseases.