As anyone who’s taken a long flight knows, sitting still for too long is a major pain. It can also present a serious health hazard, as inactivity can lead to blood clots in leg veins and the lungs. Yet this risk doesn’t affect hibernating bears, which lay still for months at a time. Now researchers know why: Hibernating bears produce less of a protein that researchers just learned helps blood to clot, the team reports today in Science.
Understanding more about this protein could have major implications for human health. When it comes to cardiovascular disorders, only heart attacks and strokes kill more people than these blood clots, which lead to a condition called deep vein thrombosis, explains Marc Rodger, a hematologist at McGill University who was not involved with the work. Current treatments and preventatives are only partially effective and involve blood thinners, he adds, which can lead to uncontrolled bleeding. “If you can develop a way to control this protein, it could be important” to treating these blood clots in humans, says Mirta Schattner, a physiologist at the National Scientific and Technical Research Council’s (CONICET’s) Institute of Experimental Medicine who was also not involved with the work.
To better understand how bears avoid dangerous blood clotting, a pair of cardiologists at the Ludwig Maximilian University of Munich, Tobias Petzold and Manuela Thienel, teamed up with a Scandinavian team and other researchers to study hibernating brown bears in Sweden.
For two winters, the researchers trekked through the snow to dig out sleeping brown bears wearing GPS collars. They tranquilized 13 bears, took blood samples, then returned the bears to their dens to finish their winter naps. The following summers, they tracked the same bears and took more blood samples. Collaborators at the Max Planck Institute of Biochemistry looked for seasonal differences in the bears’ blood that might explain why it did not clot in the winter. “It was brilliant to look at brown bears,” Schattner says. “I would never have thought of it.”
The researchers noticed a protein called HSP47 was abundant in the bears’ blood during the summer, but virtually disappeared in the winter, Thienel and her colleagues report today.
Previous work by Jon Gibbins, a cell biologist at the University of Reading, in mice had revealed that in addition to other functions, this protein sits on the surface of blood platelets involved in clot formation. Working with mice bred to lack this protein, Gibbins and his colleagues determined that platelets with less HSP47 were less likely to attract and bind to infection-fighting white blood cells called neutrophils—a key step in clot formation. “This study shows the importance of HSP47 in platelet activation,” says Nigel Mackman, who studies venous thrombosis in cancer and other diseases at the University of North Carolina, Chapel Hill.
The HSP47 on the platelets activate neutrophils, causing them to form a “net” that traps proteins, pathogens, and cells, leading to blood clots. Because hibernating bears produce less HSP47, their blood is less likely to form these nets and therefore less likely to clot, Theinel says.
Next, the researchers looked at HSP47 in people with spinal cord injuries, who—like hibernating bears—don’t seem to develop blood clots very frequently, despite being immobile for long periods of time. They found these people, too, had relatively little HSP47 compared with others who were more mobile. That suggests their bodies were toning down the production of this protein in response to being immobilized. To test that hypothesis, 10 healthy volunteers spent 27 days on bed rest while researchers monitored their HSP47 levels. Sure enough, the protein levels dropped over time. “We were really surprised that we got such a hit [with HSP47] and that it was relevant to humans,” Thienel says.
She wonders whether decreasing platelet HSP47 in people who suddenly find themselves immobilized might reduce their risk of clots until their bodies start naturally reducing the protein. But others are not yet sure of biomedical applications.
“It would be good to have these observations independently confirmed by other groups,” Mackman says.
Nonetheless, Rodger is impressed that HSP47 seems to play the same role in both bears and people, as the work suggests this clotting mechanism evolved long ago in mammals. “It’s a fascinating finding of a potential novel mechanism” to prevent clots, he points out. It may also help cancer, surgery, and trauma patients, who are at greater risk of developing clots, he adds.
“The ideal treatment for deep vein thrombosis would prevent blood clots from forming where they aren’t supposed to, while not preventing your body’s normal blood clotting machinery” as current drugs do, says Kim Martinod, a biomedical scientist at KU Leuven. “This has the potential to be just that.”
