Regulation of endothelial nitric oxide synthase expression by albumin-derived advanced glycosylation end products

We examined whether albumin-derived advanced glycosylation end products (AG Es) downregulate the expression of endothelial nitric oxide synthase (NOS). Significant reductions in NOS activity and cGMP levels in bovine aortic en dothelial cells were observed when exposed to different concentrations of a lbumin-derived AGEs, Western and Northern blot analyses showed significant decreases at the protein transcript levels. Both reductions became evident after 24 hours of exposure. Nuclear run-on assays showed that AGE-BSA did n or modify the transcription rate of the NOS III gene; however, AGE-BSA trea tment markedly reduced the half-life of NOS III mRNA. In addition, ACE-trea ted endothelial cells displayed significant reduction on their antiplatelet properties. These results indicate that NOS expression is reduced by AGEs by increasing the rate of mRNA degradation and may be relevant to the impai rment of some endothelial functions observed in diabetes and aging. The ful l text of this article is available at http://www.circresaha.org.