Vascular hypertrophy in experimental diabetes - Role of advanced glycation end products
Vascular hypertrophy in experimental diabetes - Role of advanced glycation end products
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DOI：
10.1172/jci119229
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发表时间：
1997-03-01
影响因子：
15.9
通讯作者：
Gilbert, RE
中科院分区：
文献类型：
--
作者：
Rumble, JR;Cooper, ME;Gilbert, RE
晚期糖基化终产物（AGEs）的加速形成和转化生长因子β（TGF-β）的过度表达均与糖尿病微血管和大血管并发症的发病机制有关。为了检测AGEs在这一过程中的作用，将链脲霉素诱导的糖尿病大鼠和对照动物随机接受氨基胍（AGE形成的抑制剂）或不接受治疗。在诱导糖尿病后7天、3周和8个月对动物进行研究。与对照动物相比，糖尿病与肠系膜血管重量增加和中膜壁/管腔面积增加相关，北方分析显示，TGF-β 1基因表达较对照组增加100-150%（P < 0.01），α 1（IV）胶原基因表达较对照组增加30-110%（P < 0.05）。用氨基胍治疗糖尿病大鼠导致所述病理变化的显著改善，包括TGF-β 1和α 1（IV）胶原的过度表达。这些数据暗示在TGF-β过度表达中AGEs的形成和伴随糖尿病状态的组织变化。
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.