Integrative Networks Regulating Cardiomyocyte Metabolism and Survival in Heart Failure and Insulin Resistance

European Coordinator:

• Timothy AITMAN, Imperial College, London (UK)

North American Coordinator:

• Anthony ROSENZWEIG, Beth Israel Deaconess Medical Center, Boston (USA)

Members:

The incidence of metabolic disease (obesity, metabolic syndrome, diabetes) is increasing in the developed world, and contributes to the already significant burden of cardiovascular disease.  Network researchers point out that not only do metabolic diseases increase the risk of heart disease, but heart disease usually involves some form of change in the baseline metabolism of heart cells, along with an increase in apoptosis (programmed cell death).  They hypothesize that networks of signalling exist within the heart, and that problems with these networks can lead to harmful changes in metabolism and inappropriate cell death, which appear clinically as heart failure.  One of the major goals of the network is to examine how the pathways for heart cell metabolism and survival are linked, particularly in heart failure.  For example, a general resistance in the body to the affects of insulin can diminish the ability of heart cells to repair protect or repair themselves, a condition which would lead to worsening heart failure.  At the same time, it has been discovered that heart failure, of itself, can cause cells in the heart to be resistant to insulin, which then worsens the effect.  Research into this complex process will yield new insights into cardiac disease related to metabolic disease, and into heart failure generally, and  could provide new targets for therapy in a disease that is particularly difficult to treat.