An advanced glycation endproduct cross-link breaker can reverse age-related increases in myocardial stiffness.
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
M
M
University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07103, USA.
Egan
J
J
Vasan
S
S
Jyothirmayi
G N
GN
Masurekar
M R
MR
Lopez
S
S
Williams
C
C
Torres
R L
RL
Wagle
D
D
Ulrich
P
P
Cerami
A
A
Brines
M
M
Regan
T J
TJ
D000375:Aging / Q000502:physiology*; D000818:Animals; D003971:Diastole / Q000502:physiology; D004285:Dogs; D004548:Elasticity; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D006339:Heart Rate / Q000502:physiology; D006439:Hemodynamics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D013318:Stroke Volume; D013599:Systole / Q000502:physiology; D013844:Thiazoles / Q000494:pharmacology*; D016276:Ventricular Function
D017127:Glycation End Products, Advanced; D013844:Thiazoles; C406794:alagebrium