Comparative medicine is an amazing field. Drosophila fruit flies have long been a standard in genetic research, but now, the python shows potential for developing heart medicine – or so claims a recent article in the New York Times about a paper published in Science. If you’re a little skeptical, suspend your disbelief for a moment, and delve into the amazing hypertrophy research from the University of Colorado.
Changing heart size
Hypertrophy is a term for when the heart enlarges, or thickens, from its cells expanding. It can be a healthy response to exercise, resulting in an “athlete’s heart” with an increased pumping ability, but also occurs in cardiovascular disease, where it’s a reliable indicator that the heart is doing poorly. For example, hypertrophy can occur in response to heart failure, when the heart is unable to provide an adequate blood supply to the body.
The connection to pythons is through this change in heart size. After a meal, pythons’ internal organs increase to up to twice their normal size, before eventually returning to normal without any harm to the snake. After determining that these organ size changes were due to hypertrophy, naturally researchers’ interests were piqued. What was the molecular mechanism leading to the rapid enlargement? Could it help identify mechanisms regulating cardiac growth more generally? This is the essence of how comparative medicine works – find a mechanism in a model organism, and see how it translates to our understanding of human disease.
Three fatty acids – snake oil magic
So back to the snakes. By examining compounds in the feasting pythons’ plasma, researchers were able to identify three fatty acids that together produced the same heart growth response if injected into a fasting python. Moreover, the combination was heart-specific, and didn’t lead to growth elsewhere simultaneously. A further experiment showed that when the same fatty acid combination was introduced into heart cells from rats, they developed a healthy hypertrophy, like the one found in athletes. Not only does this confirm that the mechanism isn’t unique to pythons, but also that the growth isn’t the pathological kind found in cardiovascular disease.
The final discovery – of very high interest in these days of rampant atherosclerosis (the fatty buildup inside arteries that contributes to cardiovascular disease) – was that the pythons were protected from the detriment of high lipid concentrations while they gorged. High levels of the cardioprotective enzyme superoxide dismutase (SOD) increased fatty acid transport and metabolism, and prevented unhealthy fat deposition in the heart, as would have been expected in mammals had lipids been present at similar levels.
So how does this apply to humans? The answer is, we don’t know yet. Perhaps it can lead to the development of successful drugs to treat heart failure. At the very least, the data shows that supplementing specific combinations of fatty acids can cause changes in gene expression and function in mammals. Although that might not sound too revolutionary at the moment, this is how research works – one small step at a time, to increase our overall understanding.
Written by Hanna Sofie Ellingsen at CERG.