Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-7288, USA.
Gerontology. 2012;58(3):227-37. doi: 10.1159/000334668. Epub 2012 Jan 4.
Arterial stiffening is a progressive, ubiquitous and irreversible aging process that is interwoven with and accelerated by various diseases such as diabetes, atherosclerosis and hypertension. In large arteries, aging is characterized by decreased turnover of collagen and elastin and increased advanced glycation end-products (AGEs) and cross-links. Elastic fibers undergo lysis and disorganization subsequent to their replacement by collagen and other matrix components. These events cause the loss of elasticity and induce stiffening. Conceptual approaches to minimize AGE accumulation in arteries include caloric restriction, exercise, low dietary intake of AGEs, deglycation enzymes, increased clearance of AGEs, antagonists of AGE receptors and pharmaceutical interventions. Much optimism exists in the ability of 'AGE breakers' such as alagebrium (ALT-711) to cleave AGE cross-links and reverse the age-related stiffening of arteries. However, there is little evidence that these agents actually break pre-existing AGE cross-links in vivo. In contrast, many of these anti-AGE agents share in common the ability to chelate metals, thus acting as inhibitors of metal-catalyzed AGE and protein carbonyl formation. Future work on interventions into the causes of arterial stiffness in aging needs to address more rigorously the relationship between stochastic forms of damage, such a glycation and oxidation, and the changes in elastic fiber structure thought to contribute to loss of arterial elasticity.
动脉僵硬度是一种进行性、普遍存在且不可逆转的衰老过程，它与各种疾病（如糖尿病、动脉粥样硬化和高血压）交织在一起，并加速这些疾病的发展。在大动脉中，衰老的特征是胶原蛋白和弹性蛋白的周转率降低，而晚期糖基化终产物（AGEs）和交联增加。弹性纤维在被胶原蛋白和其他基质成分取代后会发生裂解和紊乱。这些事件导致弹性丧失并引起僵硬。减少动脉中 AGE 积累的概念方法包括热量限制、运动、低 AGE 饮食摄入、脱糖化酶、AGEs 的清除增加、AGE 受体拮抗剂和药物干预。人们对“AGE 断裂剂”（如 ALT-711）能够裂解 AGE 交联并逆转与年龄相关的动脉僵硬的能力抱有很大的期望。然而，几乎没有证据表明这些药物实际上可以在体内断裂预先存在的 AGE 交联。相比之下，许多这些抗 AGE 药物都具有螯合金属的能力，因此它们是金属催化的 AGE 和蛋白质羰基形成的抑制剂。未来关于干预衰老过程中动脉僵硬原因的工作需要更严格地解决随机形式的损伤（如糖化和氧化）与弹性纤维结构变化之间的关系，这些变化被认为导致了动脉弹性的丧失。
