THE ROLE OF GLYCATION CROSS-LINKS IN DIABETIC VASCULAR STIFFENING

Previous studies have shown that biomechanical analysis of aorta from diabetic subjects reveals a marked increase in stiffness compared to a orta from age-matched control subjects. In the present paper we have p roposed that this increased stiffness can be attributed to glycation-i nduced inter-molecular cross-links based on a direct analysis of the t wo known glycation cross-links, the fluorescent pentosidine and the no n-fluorescent NFC-1. There was a sig nificant difference in the increa se in concentration of both cross-links with increasing age for both t he intima (p < 0.0025) and the media (p < 0.0005) from the diabetic co mpared to the control subjects, but no correlation with the mature enz ymic cross-link hydroxylysyl-pyridinoline. Finally, we have obtained a significant correlation of stiffness with both glycation cross-links (NFC-1, r = 0.86; p < 0.005 and pentosidine r = 0.75, p < 0.05), but t he concentration of NFC-1 is about 50 times greater than that of pento sidine, indicating that it is the major glycation crosslink responsibl e for the stiffening of the aorta.