Study of pythons could lead to new therapies for heart disease

In the first 24 hours after devouring its massive prey, the python’s heart grows 25 percent larger, its cardiac tissue softens considerably, and the organ contracts more and more forcefully, until it more than doubles its pulse rate. During this time, a vast collection of specialized genes kicks in to help increase the snake’s metabolism forty-fold. Two weeks later, once its feast has been digested, all systems return to normal, with its heart remaining only slightly larger and even stronger than before.

This extraordinary process, described by CU Boulder researchers this week in the journal PNAScould ultimately inspire new treatments for a common human heart condition called cardiac fibrosis, in which heart tissue stiffens, as well as a host of other modern diseases that the monstrous snakes seem to miraculously resist.

“Pythons can go months or even a year in the wild without eating and then ingest more than their own body mass without any harm happening to them,” said lead author Leslie Leinwand, a professor of molecular, cellular and developmental biology at CU Boulder and scientific director of the BioFrontiers Institute. “We think they have mechanisms that protect their hearts from things that would be harmful to humans. This study goes a long way toward figuring out what that is.”

Leinwand began studying pythons nearly two decades ago, and his lab remains one of the few in the world looking at these constricting, nonvenomous reptiles for clues to improving human health.

Pythons, which can grow up to 20 feet long depending on the species, typically live in resource-poor regions of Africa, South Asia and Australia. They fast for long periods of time, but when given the chance to eat, they can swallow a deer whole.

“Most people who use animal models to study disease and health typically focus on rats and mice, but there is a lot to be learned from animals like pythons that have evolved ways to survive in extreme environments,” Leinwand said.

There are two types of heart growth in humans, Leinwand explains: healthy growth, which results from chronic endurance exercise, and unhealthy growth, which results from disease.

Pythons, like elite athletes, excel at healthy heart growth.

His previous work showed that within a week to ten days after a meal, pythons’ hearts become much larger, their heart rate doubles, and their bloodstream turns milky white with circulating fats, which, surprisingly, nourish rather than damage their heart tissue.

The new study sought to understand how this all happens.

Researchers fed pythons that had fasted for 28 days a meal equal to 25 percent of their body weight and compared them to snakes that had not been fed.

They found that as the hearts of well-fed snakes grew, specialized bundles of heart muscle called myofibrils, which help the heart expand and contract, softened dramatically and contracted with about 50 percent more force. At the same time, these same snakes had “profound epigenetic differences”—that is, differences in which genes were turned on and off—compared to fasted snakes.

More research is needed to pinpoint exactly which genes and metabolites are at play and what they do, but the study suggests that some may be prompting the python’s heart to burn fat instead of sugar for fuel. Notably, diseased hearts have a harder time doing this.

Stiff or fibrous tissues promote disease in other organs besides the heart, including the lungs and liver, so there could be applications in this area as well.

“We found that the python heart is able to radically remodel itself, becoming much less rigid and much more energy efficient in just 24 hours,” Leinwand said. “If we could figure out how the python does this and harness it for therapeutic use in humans, that would be extraordinary.”