The Accumulation of the Glycoxidation Product Nε-carboxymethyllysine in Cardiac Tissues with Age, Diabetes Mellitus and Coronary Heart Disease

Heart disease is one of the most important causes of death in developed countries. N-epsilon-carboxymethyllysine (CML) is a major advanced glycation end product formed by combined reactions of non-enzymatic glycation and oxidation (glycoxidation), and it represents a general marker of oxidative stress. CML has been suggested to be involved in the pathogenesis of heart disease. Plasma CML is elevated in aging, atherosclerosis and/or diabetes. In this study, we measured cardiac CML levels to elucidate its role in the pathogenesis of heart disease. Cardiac tissues were collected from 105 patients (55.6 +/- 17.0 years old: age range, 1-78 years) undergoing cardiac surgery. The diseases comprised coronary heart disease (CHD), CHD associated with diabetes mellitus (DM), valvular heart disease and congenital heart disease. The concentration of CML in cardiac tissues of each group was 4.31 +/- 0.66, 5.29 +/- 0.59, 2.74 +/- 1.05 and 1.75 +/- 1.16 mu g/g, respectively. ELISA was used for measuring cardiac and plasma CML concentrations. Multiple linear regression analysis showed a significant positive correlation of CML concentrations with age (r = 0.803, p < 0.001), DM (r = 0.567, p < 0.001) and CHD (r = 0.523 p < 0.001). R-2 was 0.872 (p < 0.001); the three independent variables could explain 87.2% variation of CML concentrations. Cardiac CML concentrations exhibited a significant positive correlation with plasma CML (r = 0.983, p < 0.001). Our data indicate that cardiac CML concentrations increase with age, DM and/or CHD, and exhibit a positive correlation with plasma CML concentrations.