October 28, 2011
Pythons’ Huge Hearts Offer Insight For Human Heart Health
While many people think of snakes as creepy, cold-hearted creatures that swallow their prey whole. But it turns out the reptiles actually have enormous hearts that could offer clues to treating people with cardiac disease, researchers from the University of Colorado-Boulder reported on Thursday.
The surprising new study showed that the vast amounts of fatty acids circulating in the bloodstreams of feeding Burmese pythons promote healthy heart growth.
The researchers found the amount of triglycerides -- the main constituent of natural fats and oils -- in the blood of the pythons one day after eating increased by more than fifty-fold.
However, despite the massive amount of fatty acids in the pythons´ bloodstream, there was no evidence of fat deposition in the heart. Furthermore, the activity of a key enzyme known to protect the heart from damage actually increased.
After identifying the chemical make-up of blood plasma in fed pythons, CU-Boulder Professor Leslie Leinwand and her team injected fasting pythons with either "fed python" blood plasma or a reconstituted fatty acid mixture they developed to mimic such plasma.
In both cases, the pythons showed increased heart growth and indicators of cardiac health.
The researchers went one step further by injecting mice with either fed python plasma or the fatty acid mixture, with the same results.
"We found that a combination of fatty acids can induce beneficial heart growth in living organisms," said CU-Boulder postdoctoral researcher Cecilia Riquelme, first author of the report.
"Now we are trying to understand the molecular mechanisms behind the process in hopes that the results might lead to new therapies to improve heart disease conditions in humans."
As big around as telephone poles, adult Burmese pythons have been known to reach a length of 27 feet, can swallow prey as large as deer, and are able to fast for up to a year with few ill effects.
Previous studies have shown that the hearts of Burmese pythons can grow in mass by 40 percent within one to three days after a large meal, and that metabolism immediately after swallowing prey can surge by forty-fold.
Leinwand, an expert in genetic heart diseases, said there are good and bad types of heart growth.
For instance, while cardiac diseases can cause human heart muscle to thicken and decrease the size of heart chambers and heart function because the organ is working harder to pump blood, heart enlargement from exercise is actually beneficial.
"Well-conditioned athletes like Olympic swimmer Michael Phelps and cyclist Lance Armstrong have huge hearts," said Leinwand, a professor in the molecular, cellular and developmental biology department and chief scientific officer of CU's Biofrontiers Institute.
"But there are many people who are unable to exercise because of existing heart disease, so it would be nice to develop some kind of a treatment to promote the beneficial growth of heart cells."
Riquelme said once the researchers confirmed that something in the blood plasma of pythons was inducing positive cardiac growth, they began looking for the right "signal" by analyzing proteins, lipids, nucleic acids and peptides present in the fed plasma.
The team used a technique known as gas chromatography to analyze both fasted and fed python plasma blood, eventually identifying a highly complex composition of circulating fatty acids with distinct patterns of abundance over the course of the digestive process.
In the experiment with mice, the animals were hooked up to "mini-pumps" that delivered low doses of the fatty acid mixture over a period of a week. The researchers found that the mouse hearts showed significant growth in the major part of the heart that pumps blood, the heart muscle cell size increased, there were no alterations in the liver or in the skeletal muscles and there was no increase in heart fibrosis -- which makes the heart muscle more stiff and can be a sign of disease.
"It was remarkable that the fatty acids identified in the plasma-fed pythons could actually stimulate healthy heart growth in mice," said CU postdoctoral researcher Brooke Harrison, who led the mouse study.
The researchers also tested the fed python plasma and the fatty acid mixture on cultured rat heart cells, with the same positive results, she said.
The CU-led team also identified the activation of signaling pathways in the cells of fed python plasma, which serve as traffic lights of sorts, said Leinwand.
"We are trying to understand how to make those signals tell individual heart cells whether they are going down a road that has pathological consequences, like disease, or beneficial consequences, like exercise," she said.
The prey of Burmese pythons can be up to 100 percent of the constricting snake's body mass, said Leinwand.
"When a python eats, something extraordinary happens. Its metabolism increases by more than forty-fold and the size of its organs increase significantly in mass by building new tissue, which is broken back down during the digestion process,” she explained.
The three key fatty acids in the fed python plasma turned out to be myristic acid, palmitic acid and palmitoleic acid.
The enzyme that showed increased activity in the python hearts during feeding episodes, known as superoxide dismutase, is a well-known "cardio-protective" enzyme in many organisms, including humans, said Leinwand.
University of California biologist James Hicks, who has long studied pythons' extreme metabolism, called the study "very, very cool.”
If the same underlying heart signals work in animals as divergent as snakes and mice, "this may reveal a common universal mechanism that can be used for improving cardiac function in all vertebrates, including humans," he wrote in an email to USA Today.
"Only further studies and time will tell, but this paper is very exciting."
The study was funded by the National Institutes of Health and Hiberna Corp., a Boulder-based biotech firm co-founded by Leinwand that works to develop drugs based on extreme animal biology.
The study is published in the October 28 issue of the journal Science.
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