Increase in epsilon(gamma-glutamyl)lysine crosslinks in atherosclerotic aortas

Portions of aortas from normal and atherosclerotic rabbits and from human autopsy subjects were washed and separated into layers which were subjected to exhaustive proteolytic digestion. The digests were assayed for epsilon(gamma-glutamyl)lysine crosslinks by a two-stage high performance liquid chromatography (HPLC) procedure. Crosslink concentrations in intima-media from rabbits where more than 15% of the aorta lumen surface was lesioned are greater than in normal aortas or aortas with less than 15% of the surface lesioned. Higher crosslink concentrations occur in fibrolipid plaques from human aortas than in intima-media layers of equal thickness from non-lesioned areas of the same aortas. Much of the crosslink in fibrolipid plaques occurs in the proteins which float at d < 1.18 g/ml. Non-lesioned areas of intima-media from aortas with fatty streaks or plaques have higher crosslink concentrations than intima-media from aortas with no lesions. In normal and lesioned intimas thinner than 0.2 mm, the concentration of the crosslink is lower than in the subjacent media. These findings indicate that increased epsilon(gamma-glutamyl)lysine crosslinking occurs in the atherosclerotic aorta and is associated principally with smooth muscle cells. It is suggested that the crosslinked products may be involved in retention of lipoproteins and the increase in collagen production.