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 aorta from age-matched control subjects. In the present paper we have proposed that this increased stiffness can be attributed to glycation-induced inter-molecular cross-links based on a direct analysis of the two known glycation cross-links, the fluorescent pentosidine and the non-fluorescent NFC-1. There was a significant difference in the increase in concentration of both cross-links with increasing age for both the intima (p < 0.0025) and the media (p < 0.0005) from the diabetic compared to the control subjects, but no correlation with the mature enzymic cross-link hy droxylysyl-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 the concentration of NFC-1 is about 50 times greater than that of pentosidine, indicating that it is the major glycation cross-link responsible for the stiffening of the aorta.
Sims
T J
TJ
Collagen Research Group, University of Bristol, Langford, UK.
Rasmussen
L M
LM
Oxlund
H
H
Bailey
A J
AJ
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000596:Amino Acids / Q000032:analysis; D001013:Aorta, Thoracic / Q000737:chemistry* / Q000473:pathology; D001120:Arginine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D003094:Collagen / Q000032:analysis; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology*; D003925:Diabetic Angiopathies / Q000378:metabolism*; D004549:Elastin / Q000032:analysis; D017127:Glycation End Products, Advanced / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D008875:Middle Aged; D013997:Time Factors
D000596:Amino Acids; D003432:Cross-Linking Reagents; D017127:Glycation End Products, Advanced; C015484:pyridinoline; D003094:Collagen; D004549:Elastin; D001120:Arginine; C062187:pentosidine; D008239:Lysine