Formation of a dihydropyridine derivative as a potential cross-link derived from malondialdehyde in physiological systems

Malondialdehyde is a major oxidation product of lipids which is capable of cross-linking the collagen of the cardiovascular system. Identification of cross-links usually involves degradative procedures, In this paper, we use a novel, direct, approach using nuclear magnetic resonance to identify early and labile products, Initial model studies show that malondialdehyde reacts with lysine to form a dihydropyridine derivative rather than the unstable imidopropene Schiff base previously reported, The aldehydes on the pyridine ring could react further to cross-link collagen and stiffen the aorta, thereby promoting further glycation, a process that would be accelerated in diabetes. (C) 1998 Federation of European Biochemical Societies.