Vascular hypertrophy in experimental diabetes - Role of advanced glycation end products

被引：158

作者：

Rumble, JR ^{[1
]}

Cooper, ME ^{[1
]}

Soulis, T ^{[1
]}

Cox, A ^{[1
]}

Wu, L ^{[1
]}

Youssef, S ^{[1
]}

Jasik, M ^{[1
]}

Jerums, G ^{[1
]}

Gilbert, RE ^{[1
]}

机构：

[1] UNIV MELBOURNE, AUSTIN & REPATRIAT MED CTR, DEPT MED, ENDOCRINOL UNIT, HEIDELBERG, VIC 3084, AUSTRALIA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 1997年 / 99卷 / 05期

关键词：

mesenteric arteries; transforming growth factor beta; glycosylation end; products; advanced; diabetes mellitus; experimental;

D O I：

10.1172/JCI119229

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The accelerated formation of advanced glycation end products (AGEs) and the overexpression of transforming growth factor beta (TGF-beta) have both been implicated in the pathogenesis of diabetic microvascular and macrovascular complications, Previous studies in our laboratory have demonstrated that the vascular changes in diabetes include hypertrophy of the mesenteric vasculature. To examine the role of AGEs in this process, streptozotocin-induced diabetic rats and control animals were randomized to receive aminoguanidine, an inhibitor of AGE formation, or no treatment, Animals were studied at 7 d, 3 wk, and 8 mo after induction of diabetes, When compared with control animals, diabetes was associated with an increase in mesenteric vascular weight and an increase in media wall/lumen area, By Northern analysis, TGF-beta 1 gene expression was increased 100-150% (P < 0.01) and alpha 1 (IV) collagen gene expression was similarly elevated to 30-110% compared to controls (P < 0.05), AGEs and extracellular matrix were present in abundance in diabetic but not in control vessels. Treatment of diabetic rats with aminoguanidine resulted in significant amelioration of the described pathological changes including overexpression of TGF-beta 1 and alpha 1 (IV) collagen, These data implicate the formation of AGEs in TGF-beta overexpression and tissue changes which accompany the diabetic state.

引用

页码：1016 / 1027

页数：12

共 73 条

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