Mitochondrial Remodeling During Physiological Cardiac Hypertrophy in the Burmese Python
Cardiac hypertrophy occurs in response to both pathological and physiological stimuli, with the; latter providing a beneficial effect on cardiac function. In pathological hypertrophy, mitochondrial dysfunction; occurs due to oxidative stress, however, in physiological hypertrophy, sustained energy production is supported; by either mitochondrial biogenesis or via enlargement of existing mitochondria. To date, there are no approved; drugs to address mitochondrial dysfunction in heart failure. Thorough characterization of the signaling and; genetic profiles involved in metabolic remodeling during physiological hypertrophy could shed light on novel; drug targets that support energy production and potentially reverse metabolic dysfunction in the failing heart. II.; Methods and Results: Electron microscopy revealed increased area occupied and redistribution of mitochondria; in the Burmese python ventricle, a model of physiological hypertrophy, after feeding. Measurement of; phosphorylation states of 46 signaling molecules was performed and demonstrated activation of signaling; pathways that mediate both cardiac hypertrophy and mitochondrial biogenesis. To validate that mitochondrial; biogenesis is occurring, expression of 15 genes involved in mitochondrial biogenesis, mitochondrial function, and; termination of mitochondrial biogenesis was measured. Dynamic expression was observed during hypertrophy; and regression, consistent with mitochondrial biogenesis. III. Conclusions: The results suggest that physiologic; cardiac hypertrophy is supported by activation of signaling pathways that mediate mitochondrial biogenesis in; the Burmese python heart. The patterns of gene expression are consistent with this observation. Data presented; here represent a broad view of physiological metabolic remodeling in the heart as well as possible novel targets; to support contractility of the failing heart.