The accelerated formation of advanced glycation end products (AGEs) and the overexpression of transforming growth factor beta (TGF-␤ ) 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-␤ 1 gene expression was increased 100-150% ( P Ͻ 0.01) and ␣ 1 (IV) collagen gene expression was similarly elevated to 30-110% compared to controls ( P Ͻ 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-␤ 1 and ␣ 1 (IV) collagen. These data implicate the formation of AGEs in TGF-␤ overexpression and tissue changes which accompany the diabetic state. ( J.

No abstract

Despite laser photocoagulation therapy, diabetic retinopathy remains a common cause of visual impairment and blindness [1], principally as a consequence of proliferative retinopathy and macular oedema. Although the pathogenesis of these retinal disorders characterized by retinal neovascularization and exudation is incompletely understood, recent evidence has implicated the vascular endothelial growth factor (VEGF), a permeability-inducing and endothelial cell selective angiogenic glycoprotein as a key factor [2±4].Although plasma renin is suppressed in diabetes, experimental evidence suggests that the tissue reninangiotensin system (RAS) is activated in the setting of chronic hyperglycaemia [5] and that its blockade underlies the beneficial effects of angiotensin converting enzyme (ACE) inhibition in diabetic nephropathy [6] and cardiovascular disease [7]. Previous