An advanced glycation endproduct cross-link breaker can reverse age-related increases in myocardial stiffness
M Asif, J Egan, S Vasan… - Proceedings of the …, 2000 - National Acad Sciences
Proceedings of the National Academy of Sciences, 2000•National Acad Sciences
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 …
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 …
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 (≈40%) in age-related left ventricular stiffness was observed [(57.1 ± 6.8 mmHg⋅m2/ml pretreatment and 33.1 ± 4.6 mmHg⋅m2/ml posttreatment (1 mmHg = 133 Pa)]. This decrease was accompanied by improvement in cardiac function.
National Acad Sciences
