Although they spend more than half the year hibernating in freezing temperatures, brown bears (arctic ursus) remain remarkably healthy. These idle giants rarely suffer from diseases such as blood clots, which can occur in humans who experience only temporary episodes of immobility and can be fatal. “Patients who come to the hospital with a broken leg are usually susceptible to developing thrombosis,” says Tobias Petzold, cardiologist at the German Cardiovascular Research Center. “But in contrast, brown bears, which hang around for a few months, don’t develop clots.”
In a new study published Thursday in the journal SciencePetzold and his colleagues have identified a protein that helps hibernating bears avoid dangerous clotting that can prevent blood flow during their long winter sleep.
To determine how dormant bears continue to pump blood during months of torpor, Petzold and his colleagues teamed up with biologists studying a population of brown bears in Sweden. Biologists took blood samples from 13 hibernating bears in their dens during the winter. Over the summer, biologists collected additional blood from the same bears after throwing tranquilizer darts at them from a helicopter.
The researchers then subjected these samples to a battery of blood tests. They found that the amounts of more than 150 proteins varied widely between the blood of hibernating and active bears and focused on proteins in platelets – the blood components that cause clotting. The platelet protein with the greatest disparity between active and hibernating bears was heat shock protein 47 (HSP47).
HSP47 recruits an enzyme called thrombin that helps platelets stick together and form clots. In active bears, HSP47 helps repair cuts and stop bleeding. But hibernating bears, snug in their dens, have little use for this clotting protein. On average, platelets from hibernating bears produced 55 times less HSP47 protein than those from active bears.
“We hadn’t heard much about this protein and were completely surprised to find out that it had such a big impact,” says Manuela Thienel, lead author of the paper, also at the German Center for Cardiovascular Research. Thienel says decreasing levels of this particular protein likely reduces the propensity of platelets to clump together and restrict blood flow.
Mirta Schattner, a biologist at the Laboratory of Experimental Thrombosis and Immunobiology of Inflammation at the Institute of Experimental Medicine in Argentina, agrees. “This cellular interaction [of HSP47 proteins] is beneficial when limited and is [also] very important for containing infections” and inflammation, says Schattner, who was not involved with the research team but wrote a commentary on the new study in Science.
To determine if a similar mechanism prevents blood clotting in chronically immobile humans, the researchers compared blood samples from patients who had suffered debilitating spinal injuries with samples from their active counterparts. Like that of hibernating bears, the blood of chronically immobile patients contained fewer circulating HSP47 proteins. “Downregulating HSP47 during hibernation in bears or chronically immobilized patients reduces thromboinflammation” and thus reduces the risk of blood clots, Schattner explains.
The team also drew blood from several healthy people before participating in a month-long spaceflight simulation study conducted by NASA and the German Aerospace Center. After the participants experienced 27 days of head-down bed rest, the researchers collected another set of samples to see how the prolonged immobilization had impacted their physiology. The team found that the participants’ platelets began to produce significantly less HSP47 during their experimental immobilization.
The researchers found a similar pattern in the blood of mobility-impaired pigs and lab-bred mice. They postulate that reduced expression of HSP47 proteins may be a mechanism used in mammals to prevent clotting during prolonged periods of rest. But this approach appears to take time to develop – in humans, people with short-term immobility due to disease or injury are more likely to clot than chronically immobile people with brain damage. spinal cord.
Petzold says the new findings underscore how understanding the biology of bears and other animals can provide insight into how the human body works. And they could potentially inspire refined treatments to prevent clotting in patients with temporary immobility. “By examining how hibernating bears in the wild prevent clots, we now know that humans do the same to prevent blood clots,” he says.
