Penn researchers look at bird blood for clues to prevent human heart disease

One thing Chicken Little apparently didn't need to worry about was that he'd suffer a heart attack or stroke.

New work out of the University of Pennsylvania shows that chickens and other birds do not share our vulnerability to heart disease.

For humans, those diseases look like the price we pay to get a blood-clotting system that keeps us from bleeding to death every time we fumble with the kitchen knife. Chickens avoided this evolutionary trade-off by using a different blood-clotting system.

The researchers, from Penn's Perelman School of Medicine, hope that the bird blood-clotting system might give us some clues to preventing cardiovascular disease in us. They published their results in the journal Blood.

Humans and all other mammals get our clotting power from cells called platelets, said Mark Kahn, the study's senior author. These small, flat cells are crucial for our survival because our blood circulates at constant high pressure - more so than in fish, lizards, and other cold-blooded creatures. That means human blood does not just leak from cuts, but spurts.

Most platelets made in human blood live and die without doing anything, but when damage occurs, exposed proteins call collagen prompt a cascade of reactions that makes them sticky and clumpy.

That's good if you just cut yourself slicing a bagel. But it's bad if there's a rupture of artery plaque, which can lead to a deadly blockage.

Birds also have high blood pressure and need a clotting system, but they use much larger cells with a nucleus called thrombocytes. Do these pose the same cardiovascular danger as platelets?

No one had collected data on the instance of bird heart disease, so the researchers did experiments comparing chicken and human blood.

The easy part was getting the human blood. For chicken blood, the team sent colleague Alec Schmaier to a South Philadelphia market that sold live chickens. Schmaier went dozens of times, each time buying a chicken, drawing blood from the wing, and then having the chicken killed and butchered so it could become dinner for someone in the group.

Comparing the two types of clotting cells, they found both capable of manufacturing a similar set of proteins, except that birds made little to none of two proteins that are important for sticking platelets to one another.

To compare the way the bird and human blood behaved, they set up a sort of artificial artery. The substance that prompts blood clotting is collagen, which gets exposed during injuries, so they simulated this by flowing both types of blood over collagen.

The human platelets stuck to the collagen and to each other. When they used bird blood, the thrombocytes stuck to the collagen but not to each other. That suggested that bird thrombocytes can stop bleeding by forming a thin layer over the wound rather than a three-dimensional clump of the type that causes arterial clots.

The bird blood acted a lot like human blood when the human is on certain heart drugs, such as eptifibatide, also known as Integrilin, Kahn said. Such drugs work by blocking one of the receptors in our blood that is lacking in birds.

To take this study further, they induced arterial injuries in laboratory mice (representing the mammals) and parakeets (for birds).

They anesthetized the animals and then exposed the carotid artery, injecting it with a chemical called ferric chloride to simulate the damage that prompts heart attacks.

In the mouse, the platelets clumped together, blocking blood flow through the artery. In the parakeets, the blood kept flowing. Blood stuck to the sides of the artery, but did not clump up in the middle. The birds seem to have gotten a better deal than us.

This raises the question of why we have platelets if thrombocytes can do the job without the downside? All other vertebrates have thrombocytes, so these seem to be the ancestral clotting cells. Platelets may be an evolutionary innovation in the mammal group, which branched off from bird ancestors about 315 million years ago.

Could animals with platelets enjoy some unseen advantage? Kahn speculates that mammals' clumping makes them a little better at healing wounds. Early mammals may have needed better blood-clotting ability to survive than did birds, since the fossil record shows that for million of years, mammals were small and lived among hungry dinosaurs. Some dinosaurs were the ancestors of modern birds.

The study does not tell us if this is why we mammals got platelets instead of thrombocytes, said Andrew Read, a Pennsylvania State University biologist who applies evolution to medical questions. Still, he likes how the Penn team approached medical questions from an evolutionary angle - something few researchers do.

"I keep wondering: How many Americans die each year because evolution is so poorly taught at schools?" Read said. "How many causes and cures of disease are being missed because physicians can't see the world through an evolutionary lens? . . . Sadly, I think it will all be much clearer in 50 years."