The role of glycation cross-links in diabetic vascular stiffening

Summary

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 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 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.

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Abbreviations

AGE:

Advanced glycation end-product

FFI:

furoyl-furanyl imidazole

HHL:

histidino-hydroxylysinonor-leucine

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Sims, T.J., Rasmussen, L.M., Oxlund, H. et al. The role of glycation cross-links in diabetic vascular stiffening. Diabetologia 39, 946 (1996). https://doi.org/10.1007/BF00403914

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Keywords

  • Diabetes mellitus
  • glycation
  • cross-links
  • vascular stiffening