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Endothelial cell dysfunction in type I and II diabetes: The cellular basis for dysfunction
Author(s) -
Pannirselvam Malarvannan,
Anderson Todd J.,
Triggle Chris R.
Publication year - 2003
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10127
Subject(s) - endothelial dysfunction , tetrahydrobiopterin , enos , oxidative stress , nitric oxide , endocrinology , medicine , polyol pathway , chemistry , endothelium , bradykinin , glycation , nitric oxide synthase , endothelial stem cell , vasodilation , superoxide , diabetes mellitus , pharmacology , biochemistry , receptor , enzyme , aldose reductase , in vitro
Micro‐ and macrovascular complications are the leading causes of mortality in Types I and II diabetes. Hyperglycemia results in increased advanced glycosylation end (AGE) products, oxidative stress, increased sorbitol levels, and increased activation of protein kinase C. These effects of hyperglycemia eventually lead to impaired endothelium‐dependent relaxation to vasoactive substances such as acetylcholine and bradykinin. Increased oxidative stress, which will reduce levels of nitric oxide (NO), and/or decreased bioavailability of tetrahydrobiopterin (BH 4 ), a cofactor for endothelial NO synthase (eNOS), may lead to a phenomenon called “uncoupling” of eNOS and this leads to endothelial dysfunction. Uncoupled NOS produces superoxide anions which lead to a further reduction in NO bioavailability. Thus, restoring BH4 levels and antioxidant activity could prove to be novel approaches for the treatment of endothelial dysfunction in Type I and II diabetes. Drug Dev. Res. 58:28–41, 2003. © 2003 Wiley‐Liss, Inc.