An advanced glycation endproduct cross-link breaker can reverse age-related increases in myocardial stiffness

Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2809-13. doi: 10.1073/pnas.040558497.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Diastole / physiology
  • Dogs
  • Elasticity
  • Glycation End Products, Advanced / antagonists & inhibitors*
  • Heart Rate / physiology
  • Hemodynamics
  • Male
  • Myocardium / metabolism*
  • Stroke Volume
  • Systole / physiology
  • Thiazoles / pharmacology*
  • Ventricular Function


  • Glycation End Products, Advanced
  • Thiazoles
  • alagebrium