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Inverse
Inverse
Science
Jennifer Walter

Hibernating Bears Reveal How to Prevent Blood Clots in Humans


It’s impressive enough that bears can go for months without food or water, hibernating in a low-energy state called torpor to get through the winter.

But on top of that, bears aren’t plagued with cardiovascular problems as they lie still for months on end. For humans, an increased risk of blood clots, high blood pressure, and heart disease is normal fare when we’re sedentary for long periods of time — hence the adage that sitting is the new smoking.

“[Brown] bears hibernate for almost half a year — usually five to seven months,” Manuela Thienel, a cardiologist at the University Hospital of Ludwig-Maximilians-University Munich, tells Inverse. That makes them “a very good translational model for [the sedentary], or very immobile lifestyle” that many people live.

Scientists have long been interested in how hibernating bears, as well as some people with long-term injuries, keep their risk of blood clots low despite extended periods of inactivity.

Today, Thienel and colleagues present an answer in the journal Science, showcasing how bears, humans, and other mammals naturally prevent blood clots thanks to an important protein in the blood.

Hibernation secrets

While bears seem to hibernate each winter without a hitch, there isn’t a lot of documented data on how their heart health fares after the long months of stillness.

Tobias Petzold, a cardiologist at the Ludwig-Maximilians-University of Munich and co-author on the new study, tells Inverse that he was approached by a colleague a few years ago who wanted to investigate why hibernating brown bears didn’t seem to develop deep-vein thrombosis — a common condition where blood clots form deep in the veins.

“We [were] pretty much fascinated by this question, because I think it's some kind of obvious assumption,” says Petzold, who works at the University Hospital of LMU Munich. “Everyone thinks that it has to be like this, but no one actually showed it and proved it, and how it works.”

So to test out their hypothesis, the researchers needed some bears to study. In February 2019, they tagged along with a team of experts involved with the Scandinavian Brown Bear Research Project to gather blood samples from 13 brown bears hibernating in Sweden.

After collecting the winter samples, the researchers returned in the summer for another bear capture. Then, they took the bear blood to the lab to test if the animals formed any blood clots, and what changed in their bodies during the seasons.

Matters of the Heart

The bear’s D-dimer levels — protein fragments that indicate the presence of serious blood clots — were much lower in the winter than the summer. And none of them experienced a pulmonary embolism, which is a serious condition where a blood clot can break off from a vein and travel to the lungs.

Autopsies of deceased bears showed that they do sometimes experience blood clots during active months, and they were more likely to die during the summer than the winter. When the bears were hibernating, their mortality rate was a mere .4 percent, but during active months, that number jumped to a whopping 58.4 percent.

Their risk of death in general was much, much higher when they were out and about — which fueled more questions about how the bears could withstand months of stillness with no serious cardiovascular effects.

To find answers, the researchers took a closer look at proteins in the bears’ blood. One change that stood out was their level of heat shock protein 47 (HSP47), which plays a role in getting blood platelets to clot together. It was 55 times less abundant in hibernating bears than active ones.

“It was a really, really clear separation between hibernation and active state,” Petzold says. The bears were able to switch off their production of HSP47 between seasons, which drastically changed their risk of blood clots.

But the team’s investigation didn’t stop with the bears — they wanted to see if HSP47 levels changed in other sedentary mammals, including humans.

A Common Trend

There’s a bit of a paradox when it comes to blood clot risk in people.

“Short-term immobility, like breaking your leg [and] going into the hospital, increases your risk of thrombosis,” Petzold explains. But if you’re chronically immobile from a spinal cord injury, for example, you’re no more likely to develop a blood clot than the rest of the population.

Having found that HSP47 was the likely driver of lower blood clot risk in bears, the researchers looked for it in human patients as well. Sure enough, people with spinal cord injuries had much lower levels of the protein than those who were not injured.

And in one experiment, the researchers analyzed blood samples from people who were not chronically injured, but were instructed to lay still for 27 days. At the end of the trial, their levels of HSP47 began to tank, showing how the body adapted to prevent blood clots in the event of long-term stillness.

Experiments with pigs and mice also showed similar results — lower blood clot risk seemed tied to lower levels of HSP47.

Future cures

Knowing that HSP47 likely changes blood clot risk could one day lead to treatments to prevent deep vein thrombosis and pulmonary embolism, which millions of people develop every year. But Petzold says there’s still a need for more information on how, exactly, the body naturally prevents blood clots.

“I think there's some research that has to be done before we can really go into drug development,” he says. Right now, researchers have a basic understanding of how HSP47 expression changes on a cellular level, but they need to get more nuanced with what’s happening in the body at a molecular level.

However, the current study, which was a collaboration between dozens of researchers and institutions, presents a new angle to our understanding of blood clot risk. Petzold calls the collaboration unconventional, since it took expertise from biologists, clinicians, biochemists, veterinarians, and more to answer the big questions in bears and beyond.

“It was a really, really broad project,” he adds.

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