Some vertebrates evolved to have a remarkable capacity for anatomical and physiological plasticity in response to environmental challenges. One example of such plasticity can be found in the ambush-hunting snakes of the genus Python, which exhibit reversible cardiac growth with feeding. The predation strategy employed by pythons is associated with months-long fasts that are arrested by ingestion of large prey. Consequently, digestion compels a dramatic increase in metabolic rate and hypertrophy of multiple organs, including the heart. In this Review, we summarize the post-prandial cardiac adaptations in pythons at the whole-heart, cellular and molecular scales. We highlight circulating factors and cellular signaling pathways that are altered during digestion to affect cardiac form and function and propose possible mechanisms that may drive the post-digestion regression of cardiac mass. Adaptive physiological cardiac hypertrophy has also been observed in other vertebrates, including in fish acclimated to cold water, birds flying at high altitudes and exercising mammals. To reveal potential evolutionarily conserved features, we summarize the molecular signatures of reversible cardiac remodeling identified in these species and compare them with those of pythons. Finally, we offer a perspective on the potential of biomimetics targeting the natural biology of pythons as therapeutics for human heart disease.

Funding

T.G.M. acknowledges support from the National Institutes of Health (F32 HL170637). L.A.L. acknowledges support from the National Institutes of Health (R01 GM029090) and the Leducq Foundation (Cardiac Splicing as a Therapeutic Target – CASTT). Deposited in PMC for release after 12 months.

Special Issue

This article is part of the Special Issue ‘The integrative biology of the heart’, guest edited by William Joyce and Holly Shiels. See related articles at https://journals.biologists.com/jeb/issue/227/20.

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