Basta G, De Caterina R
Istituto di Fisiologia Clinica-C.N.R., Pisa.
G Ital Cardiol. 1996 Jun;26(6):699-719.
The formation of advanced glycosylation end-products (AGEs) is an important biochemical abnormality that accompanies diabetes mellitus. Advanced glycosylation is a process resulting from the spontaneous covalent reaction of circulating glucose with free amino groups of several proteins. Subsequent rearrangement reactions produce fluorescent moieties that remain irreversibly bound to proteins. In this review we summarize and discuss recent studies indicating that effects of AGEs on vascular wall homeostasis may account for the rapidly progressive atherosclerosis associated with diabetes mellitus. Within the vascular wall, collagen-linked AGEs "trap" plasma proteins, quench nitric oxide activity, and interact with specific macrophage receptors to induce cytokine and growth factor release. On plasma low density lipoproteins (LDL), AGEs initiate oxidative reactions that promote the formation of oxidized LDL. Interaction of AGEs with endothelial cells produce an increase in vascular permeability, the expression of procoagulant activity, and the generation of oxidative stress resulting in increased endothelial expression of adhesion molecules for leukocytes. Since early steps of atherosclerosis involve alterations of blood-vessel wall interactions initiating an inflammatory-proliferative process, a better understanding of the biochemical mechanisms by which AGEs contribute to this process, could be relevant to devise preventive and therapeutic strategies for atherosclerosis in diabetes.
晚期糖基化终末产物（AGEs）的形成是糖尿病伴随的一种重要生化异常。晚期糖基化是循环葡萄糖与多种蛋白质的游离氨基发生自发共价反应的过程。随后的重排反应产生荧光部分，这些荧光部分会不可逆地与蛋白质结合。在本综述中，我们总结并讨论了近期的研究，这些研究表明AGEs对血管壁稳态的影响可能是糖尿病相关快速进展性动脉粥样硬化的原因。在血管壁内，与胶原蛋白相连的AGEs“捕获”血浆蛋白，抑制一氧化氮活性，并与特定的巨噬细胞受体相互作用以诱导细胞因子和生长因子释放。在血浆低密度脂蛋白（LDL）上，AGEs引发氧化反应，促进氧化LDL的形成。AGEs与内皮细胞相互作用会导致血管通透性增加、促凝血活性表达增加以及氧化应激的产生，从而导致内皮细胞上白细胞黏附分子的表达增加。由于动脉粥样硬化的早期步骤涉及血管壁相互作用的改变，引发炎症增殖过程，更好地理解AGEs促成这一过程的生化机制，可能有助于制定糖尿病动脉粥样硬化的预防和治疗策略。
