Novel Mechanistic Insights into the Role of Advanced Glycation End Products in the Development of Diabetic Cardiomyopathy

Abstract

Advanced glycation end products (AGEs) are molecules formed through the nonenzymaticglycation of proteins and are central to the development of cardiovascularcomplications of diabetes including heart failure. AGEs influence cellular function throughthe cross-linking of cellular proteins as well as through actions on cell surface receptors,the most common of which is (RAGE). However, it is still unclear whether AGEs contributeto myocardial abnormalities observed in diabetes through direct myocardial actionsmediated through the RAGE receptor and if so, their underlying mechanisms of action. Wehave therefore investigated the effects of AGEs on calcium handling in isolated adultmouse cardiomyocytes and cultured neonatal rat cardiomyocytes (NRCM) andcharacterised their underlying mechanisms of action in NRCM.Standard molecular techniques were used. Western blot showed expression of RAGEreceptor in mouse whole heart tissue and in both NRCM and adult mouse cardiomyocytes.Incubation of NRCM for 24 hours with AGEs showed a dose dependant reduction ofcalcium transient amplitude with a maximum of 50% at 1 g/l (P

Date of Award	1 Aug 2012
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Mamas Mamas (Supervisor)