BREAKERS OF ADVANCED GLYCATION END-PRODUCTS RESTORE LARGE ARTERY PROPERTIES IN EXPERIMENTAL DIABETES

Glucose and other reducing sugars react with proteins by a nonenzymati c, posttranslational modification process called nonenzymatic glycatio n. The formation of advanced glycation end products (AGEs) on connecti ve tissue and matrix components accounts largely for the increase in c ollagen crosslinking that accompanies normal aging and which occurs at an accelerated rate in diabetes, leading to an increase in arterial s tiffness. A new class of AGE crosslink ''breakers'' reacts with and cl eaves these covalent, AGE-derived protein crosslinks. Treatment of rat s with streptozotocin-induced diabetes with the AGE-breaker ALT-711 fo r 1-3 weeks reversed the diabetes-induced increase of large artery sti ffness as measured by systemic arterial compliance, aortic impedance, and carotid artery compliance and distensibility. These findings will have considerable implications for the treatment of patients with diab etes-related complications and aging.