Cardiac hypertrophy in Burmese pythons may aid treatment of human cardiac disease

Claire Williams, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0SP

Mammalian hearts undergo hypertrophy in two distinct settings. Firstly hypertrophy can occur pathologically, in response to stimuli such as a myocardial infarction or chronic hypertension. This type of hypertrophy is detrimental to cardiac function and is associated with, amongst other features, an increase in apoptosis and fibrosis and a fetal pattern of gene expression. Secondly, hypertrophy can be physiological, for example as a response to exercise. This type of hypertrophy is thought to be mediated by insulin-like growth factor 1 (IGF-1) signalling and is protective against pathological stimuli to cardiac hypertrophy. A remarkable example of physiological cardiac hypertrophy occurs in the Burmese python which experiences a 40% increase in cardiac size within 72 hours of eating a meal. The mechanism underlying this response is the subject of a paper in this week’s Science (1).

In order to determine if a circulating factor was responsible for python cardiac hypertrophy, fed python plasma was added to rat ventricular myocytes in culture. These myocytes showed a significant increase in size and an altered pattern of gene expression which resembled that seen in the python heart. The python plasma retained the ability to cause these changes following heating and proteinase treatment, suggesting a lipid species was responsible. Mass spectrometry of plasma from pre and post prandial pythons showed a complex pattern of fatty acid expression. A mixture of myristic acid, palmitic acid and palmitoleic acid was determined to likely be responsible for the effects. This mixture was infused into fasted pythons and resulted in cardiac hypertrophy as effectively as a meal. The fatty acid mixture was then infused into mice over a 7 day period. The mice showed a significant increase in left ventricular mass due to an increase in cardiomyocyte cross sectional area. There was no fetal gene expression, no alteration in apoptosis or lipid deposition and no effect on the mass of the liver or skeletal muscle in these mice. A mixture of three other fatty acids found in pythons had no effect on cardiac size.

In conclusion this paper shows that a mixture of fatty acids, elucidated from studies into cardiac hypertrophy in Burmese pythons, is capable of causing physiological hypertrophy in mammalian cardiomyocytes. This has potential applications in the prevention and management of pathological cardiac hypertrophy in humans.

References: 

1. Riquelme CA, Magida JA, Harrison BC, Wall CE, Marr TG, Secor SM, Leinwand LA. Fatty Acids Identified in the Burmese Python Promote Beneficial Cardiac Growth. Science 2011 Oct;334(6055):528 -531.
doi: 10.1126/science.1210558

Story image from Wikimedia Commons.