Cooper M E, Bonnet F, Oldfield M, Jandeleit-Dahm K
Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, West Heidelberg, Victoria, Australia.
Am J Hypertens. 2001 May;14(5 Pt 1):475-86. doi: 10.1016/s0895-7061(00)01323-6.
Diabetes is commonly associated with both microvascular and macrovascular complications. These vascular complications are accelerated in the context of systemic hypertension. During the past few years the underlying molecular mechanisms responsible for diabetic vascular complications have begun to be clarified. It appears that both metabolic and hemodynamic factors interact to stimulate the expression of cytokines and growth factors in the various vascular trees. Overexpression of the prosclerotic cytokine transforming growth factor-beta has been observed in glomeruli and tubules from the diabetic kidney. In the retina the angiogenic cytokine vascular endothelial growth factor and its receptor, vascular endothelial growth factor R-2 are increased in experimental diabetes. These changes in growth factors are viewed to be responsible for the extracellular matrix accumulation in the diabetic kidney and new vessel formation in the diabetic retina. Changes in cytokines have also been observed at other vascular sites including the mesenteric vascular tree. Vasoactive hormones, such as angiotensin II and endothelin, are potent stimulators of cytokines with recent studies showing that inhibitors of these vasoactive hormone pathways may confer organ protection in diabetes by inhibition of growth factor expression. Glucose-dependent factors, such as the formation of advanced glycation end products that interact with specific receptors and lead to overexpression of a range of cytokines, may play an important role in diabetic vascular complications including atherosclerosis. It is likely that the effects of inhibitors of this pathway such as aminoguanidine on cytokine production may play a pivotal role in mediating the renal, retinal, and vasoprotective effects observed with this agent in experimental diabetes. It is anticipated that the advent of specific inhibitors of cytokine formation or action will provide new approaches for the prevention and treatment of diabetic vascular complications.
糖尿病通常与微血管和大血管并发症相关。在系统性高血压的情况下，这些血管并发症会加速发展。在过去几年中，导致糖尿病血管并发症的潜在分子机制已开始得到阐明。似乎代谢和血流动力学因素相互作用，刺激各种血管系统中细胞因子和生长因子的表达。在糖尿病肾病的肾小球和肾小管中已观察到促硬化细胞因子转化生长因子-β的过度表达。在视网膜中，实验性糖尿病时血管生成细胞因子血管内皮生长因子及其受体血管内皮生长因子R-2会增加。这些生长因子的变化被认为是糖尿病肾病中细胞外基质积累和糖尿病视网膜中新血管形成的原因。在包括肠系膜血管系统在内的其他血管部位也观察到了细胞因子的变化。血管活性激素，如血管紧张素II和内皮素，是细胞因子的强效刺激物，最近的研究表明，这些血管活性激素途径的抑制剂可能通过抑制生长因子表达在糖尿病中赋予器官保护作用。葡萄糖依赖性因素，如晚期糖基化终产物的形成，其与特定受体相互作用并导致一系列细胞因子的过度表达，可能在包括动脉粥样硬化在内的糖尿病血管并发症中起重要作用。这条途径的抑制剂，如氨基胍，对细胞因子产生的影响可能在介导该药物在实验性糖尿病中观察到的肾脏、视网膜和血管保护作用方面起关键作用。预计细胞因子形成或作用的特异性抑制剂的出现将为糖尿病血管并发症的预防和治疗提供新方法。
