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Age‐dependent diabetes induces endothelial dysfunction: the role of VEGF and TGF‐beta
Author(s) -
Eatman Danita,
Stokley Cyrenah,
McKenzie India,
Bayorh Mohamed
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.990.28
Subject(s) - medicine , endocrinology , diabetes mellitus , prostacyclin , vascular endothelial growth factor , streptozotocin , endothelial dysfunction , nitric oxide , downregulation and upregulation , transforming growth factor beta , transforming growth factor , endothelium , vegf receptors , chemistry , biochemistry , gene
Transforming growth factor (TGF) ‐ beta and vascular endothelial growth factor (VEGF) have been implicated in the endothelial dysfunction and the vasculopathy of diabetes; however, the specific mechanisms involved in the vasculopathic effect of these growth factors have not been clearly elucidated. Therefore, we hypothesized that diabetes induced by streptozotocin (STZ) leads to a reduction in endothelium‐derived relaxing agents, which may be caused by upregulation of VEGF and/or TGF‐beta in an age‐dependent manner. To test the hypothesis, young (4‐5 weeks old) and mature (>7 months old) male Sprague‐Dawley rats were given a single injection of STZ to induce diabetes. Survival rate was age‐dependent [young (100%) vs. old (50%)]. The increase in blood glucose levels had no effect on blood pressure. Plasma nitric oxide and prostacyclin levels were reduced by 20% and 45% respectively in the young diabetic rats. STZ increased plasma thromboxane A 2 levels in both groups. Furthermore, STZ amplified VEGF expression in both groups; however, only the mature rats showed a significant change in TGF‐beta expression. Taken together, these findings indicate that diabetes induced endothelial dysfunction/mortality is greater in older rats and due to the over expression of both TGF‐beta and VEGF. This research was funded, in part, by NIDDK grant 1SC1DK082385‐01.