An advanced glycation endproduct cross-link breaker can reverse age-related increases in myocardial stiffness
An advanced glycation endproduct cross-link breaker can reverse age-related increases in myocardial stiffness
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DOI：
10.1073/pnas.040558497
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发表时间：
2000-03-14
影响因子：
11.1
通讯作者：
Regan, TJ
中科院分区：
文献类型：
--
作者：
Asif, M;Egan, J;Regan, TJ
心血管系统弹性降低是哺乳动物正常衰老过程的标志之一。这种弹性降低的一个潜在解释是，葡萄糖可以与长寿命的蛋白质，如胶原和晶状体晶体蛋白，发生非酶反应，并将它们连接在一起，产生晚期糖基化终末产物(AGEs)。此前的研究表明，氨基胍是一种AGE抑制剂，可以防止蛋白质的葡萄糖交联以及与衰老和糖尿病相关的弹性丧失。最近，一种AGE交联剂(ALT-711)已经被描述，我们已经在老年狗身上进行了评估。服用ALT-711 1个月后，与年龄相关的左心室硬度显著降低(约40%)[(57.1+/-6.8 mm Hg.m(2)/ml治疗前和33.1+/-4.6 mm Hg.m(2)/ml治疗后(1 mm Hg=133Pa.)]。这一下降伴随着心功能的改善。
Decreased elasticity of the cardiovascular system is one of the hallmarks of the normal aging process of mammals. A potential explanation for this decreased elasticity is that glucose can react nonenzymatically with long-lived proteins, such as collagen and lens crystallin, and link them together, producing advanced glycation endproducts (AGEs). Previous studies have shown that aminoguanidine, an AGE inhibitor, can prevent glucose cross-linking of proteins and the loss of elasticity associated with aging and diabetes. Recently, an AGE cross-link breaker (ALT-711) has been described, which we have evaluated in aged dogs. After 1 month of administration of ALT-711, a significant reduction (approximate to 40%) in age-related left ventricular stiffness was observed [(57.1 +/- 6.8 mmHg.m(2)/ml pretreatment and 33.1 +/- 4.6 mmHg.m(2)/ml posttreatment (1 mmHg = 133 Pa)]. This decrease was accompanied by improvement in cardiac function.