Nearly 65 million Americans suffer from some form of heart disease and the cost to society is estimated to be >$350 billion/year. Within the spectrum of heart disease, enlargement of the heart, also termed cardiac hypertrophy, is a major risk factor for premature cardiovascular morbidity and mortality.

In contrast to pathological hypertrophy, physiological hypertrophy of the heart as a consequence of exercise is associated with beneficial patterns of gene expression and improved cardiac function. Importantly, evidence suggests that physiological cardiac growth induced by exercise can promote a protective cardiac response in the face of pathological stimuli such as pressure overload.

Currently available therapies for the treatment of heart failure are largely palliative and there are no drugs capable of promoting beneficial patterns of cardiac growth and gene expression in the face of pathological stimuli. Given this large unmet need, we believe that novel strategies for promoting beneficial cardiac adaptation in the face of pathological stimuli will have significant commercial potential.

We have used an animal model of extreme physiological cardiac adaptation, the postprandial Burmese python, to identify novel regulators of beneficial cardiac growth. As an infrequent feeder, the python exhibits a dramatic metabolic response to a meal, with a ~35-fold increase in overall metabolic rate observed in the first few days after a meal (Secor and Diamond 1995; Secor and Diamond 1997; Secor and Diamond 1998). In response to this extreme increase in metabolic demand, there is robust organ growth including cardiac hypertrophy (Secor and Diamond 1998; Andersen, Rourke et al. 2005).

In our characterization of the python model, we have identified novel combinations of circulating fatty acids (FAs) that recapitulate the cardiac growth seen in response to an intact rodent meal. We have shown that the FAs identified in the fed python promote beneficial cardiomyocyte hypertrophy in vitro (NRVMs) and in vivo (pythons and mice).