Python's Bulging heart offers clues For human heart disease treatment

The Burmese python is a remarkable creature: it doesn't eat for a year with few ill effects, and then swallows prey like deer with a body mass that approaches 100% of its own. When it does this, its heart swells by as much as 40% over the ensuing 72 hours. Now scientists from the University of Colorado Boulder have found that huge amounts of fatty acids circulating in the bloodstream of pythons as they feed promote healthy heart growth, and this may offer some clues for treating human heart disease. Leslie Leinwand and her research team at the University of Colorado Boulder (CU Boulder) in the US found the amount of triglycerides, the main constituent of natural fats and oils, in the bloodstream of Burmese pythons can rise more than 50-fold in the blood just 24 hours after eating. You can read about their findings online in the 28 October issue of Science, where they describe how despite this massive increase in fatty acids in the python's bloodstream, they could find no evidence of fat deposited in the heart. They did however, find increased activity in an important enzyme known to protect the heart from damage. Leinwand, who holds a Marsico Endowed Chair of Excellence at CU-Boulder and is a professor in the molecular, cellular and developmental biology department and chief scientific officer of CU's Biofrontiers Institute, told the press: "When a python eats, something extraordinary happens. Its metabolism increases by more than fortyfold and the size of its organs increase significantly in mass by building new tissue, which is broken back down during the digestion process." For their study, Leinwand and colleagues investigated the molecular mechanisms behind the reptile's remarkable physiological heart growth. Their goal was to find out what might be applicable to the mammalian heart. First they identified the chemical make up of the blood plasma in pythons that had been fed. Then they injected pythons that had not eaten for some time with either the same blood plasma as in the blood of pythons that are feeding, or with a made up fatty acid mix they developed to mimic such plasma. They found that in both cases, the pythons's heart grew and showed indicators of cardiac health Then to test the effect in mammals, they injected lab mice with either fed python plasma or the made up mix, and got the same results. They did not give the mice the plasma all in one go, but hooked them up to "mini-pumps" so they received low doses of the fatty acid mix over a week. They found that the mouse hearts not only grew significantly in the part that pumps blood, but also the heart muscle cell size increased. And this happened with no accompanying increase in heart fibrosis, which stiffens heart muscle and can be a sign of disease. There were no changes in the liver or the skeletal muscles. They repeated the tests on cultured rat heart cells and found the same results. First author Cecilia Riquelme, CU-Boulder postdoctoral researcher, said: "We found that a combination of fatty acids can induce beneficial heart growth in living organisms." "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," she added. Leinwand is an expert in genetic heart diseases including hypertrophic cardiomyopathy, the leading cause of sudden death in young athletes. She explained there are good and bad types of heart growth: that which occurs in heart disease, where the heart muscle thickens, reducing the size of the heart chambers and making the heart have to work harder to pump blood, and that which occurs as a result of exercise, which enlarges the heart and is beneficial. "Well-conditioned athletes like Olympic swimmer Michael Phelps and cyclist Lance Armstrong have huge hearts," said Leinwand. "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," she added. Once they confirmed that something in the python's blood plasma was promoting beneficial cardiac growth, they began to investigate the molecular signalling. Using gas chromatography, they analyzed proteins, lipids, nucleic acids and peptides in the plasma of the fed and the fasting pythons. They eventually found a complex mixture of circulating fatty acids, whose levels changed in distinct patterns as digestion ensued. Leinwand said they also identified the activation of signalling pathways in the cells of fed python plasma that act as a sort of traffic light system: "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. Leinwand and colleagues write in their Science paper: "We found that heart growth in pythons is characterized by myocyte hypertrophy in the absence of cell proliferation and by activation of physiological signal transduction pathways. Despite high levels of circulating lipids, the postprandial python heart does not accumulate triglycerides or fatty acids. Instead, there is robust activation of pathways of fatty acid transport and oxidation combined with increased expression and activity of superoxide dismutase, a cardioprotective enzyme." The key fatty acids in the fed python plasma were myristic acid, palmitic acid and palmitoleic acid. The enzyme superoxide dismutase is known to be cardioprotective in many organisms, including humans, said Leinwand.