Administration of the AGE cross-link breaker ALT-711 for 1 month in aged dogs significantly reduced age-related left ventricular stiffness by approximately 40%.
Effect estimate: 40% reduction
Absolute Event Rate: 33.1% vs 57.1%
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 ( approximately 40%) in age-related left ventricular stiffness was observed (57.1 +/- 6.8 mmHg x m(2)/ml pretreatment and 33.1 +/- 4.6 mmHg x m(2)/ml posttreatment (1 mmHg = 133 Pa). This decrease was accompanied by improvement in cardiac function.
Asif et al. (Tue,) conducted a other in Age-related myocardial stiffness. ALT-711 vs. Pretreatment was evaluated on Left ventricular stiffness (40% reduction). Administration of the AGE cross-link breaker ALT-711 for 1 month in aged dogs significantly reduced age-related left ventricular stiffness by approximately 40%.