Glycosaminoglycans, hyperglycemia, and disease.
CONCLUSIONS
Diabetes is a widespread disease with many clinical pathologies. Despite numerous pharmaceutical strategies for treatment, the incidence of diabetes continues to increase. Hyperglycemia, observed in diabetes, causes endothelial injury resulting in microvascular and macrovascular complications such as nephropathy, retinopathy, neuropathy, and increased atherosclerosis.


BACKGROUND
Proteoglycans are chemically diverse macromolecules consisting of a protein core with glycosaminoglycans (GAGs) attached. Heparan sulfate proteoglycans are important compounds found on the endothelial cell membrane and in the extracellular matrix, which play an important role in growth regulation and serve as a reservoir for cytokines and other bioactive molecules. Endothelial cells are altered in hyperglycemia by a reduction in heparan sulfate and upregulation and secretion of heparanase, an enzyme that degrades heparan sulfate GAGs on proteoglycans. Reactive oxygen species, increased in diabetes, also destroy GAGs.


RESULTS
Preservation of heparan sulfate proteoglycans on endothelial cells may be a strategy to prevent angiopathy associated with diabetes. The use of GAGs and GAG-like compounds may increase endothelial heparan sulfate and prevent an increase in the heparanase enzyme.


CONCLUSIONS
Elucidating the mechanisms of GAG depletion and its significance in endothelial health may help to further understand, prevent, and treat cardiovascular complications associated with diabetes. Further studies examining the role of GAGs and GAG-like compounds in maintaining endothelial health, including their effect on heparanase, will determine the feasibility of these compounds in diabetes treatment. Preservation of heparan sulfate by decreasing heparanase may have important implications not only in diabetes, but also in cardiovascular disease and tumor biology.
1 Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan , Saskatoon, Canada .
Linda M
LM
Hiebert
Juying
J
Han
Anil Kumar
AK
Mandal
D000818:Animals; D048909:Diabetes Complications / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000378:metabolism*
D006025:Glycosaminoglycans; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate