Mitochondrial Dynamics in Cardiovascular Medicine

Anisha A. Gupte PhD, Dale J. Hamilton MD, FACP, Anisha A. Gupte, Dale J. Hamilton

Gaetano Santulli

Provision for the continuous demand for energy from the beating heart relies heavily on efficient mitochondrial activity. Non-ischemic cardiomyopathy in which oxygen supply is not limiting results from etiologies such as pressure overload. It is associated with progressive development of metabolic stress culminating in energy depletion and heart failure. The mitochondria from the ventricular walls undergoing non-ischemic cardiomyopathy are subjected to long periods of adaptation to support the changing metabolic milieu, which has been described as mal-adaptation since it ultimately results in loss of cardiac contractile function. While the chronicity of exposure to metabolic stressors, co-morbidities and thereby adaptive changes in mitochondria maybe different between ischemic and non-ischemic heart failure, the resulting pathology is very similar, especially in late stage heart failure. Understanding of the mitochondrial changes in early-stage heart failure may guide the development of mitochondrial-targeted therapeutic options to prevent progression of non-ischemic heart failure. This chapter reviews findings of mitochondrial functional changes in animal models and humans with non-ischemic heart failure. While most animal models of non-ischemic heart failure exhibit cardiac mitochondrial dysfunction, studies in humans have been inconsistent despite confirmed reduction in ATP production. This chapter also reviews the possibility of impairment of substrate supply processes upstream of the mitochondria in heart failure, and discusses potential metabolism-targeted therapeutic options.