17 April 2023

Reducing a key protein could help to prevent the formation of blood clots, according to a new study which used hibernating bears to identify naturally protective mechanisms.

An international team, led by researchers from Germany and Sweden, identified a significant reduction in the Hsp47 protein in the platelets of bears, mice, pigs, and humans when they are still for months or even years at a time. The team also showed that Hsp47 reduction prevents the formation of blood clots.

The study, published last week in Science, first identified the reduction in Hsp47 in hibernating bears; levels of the protein are reduced by 55 times in hibernating bears compared to when bears are active during the spring and summer.

The researchers say their findings could lead to new medicines to help those who have inherited blood clotting disorders that put them at risk for pulmonary embolism, heart attack, and stroke.

Professor Jon Gibbins, one of the study researchers based at the University of Reading, said: “It seems counterintuitive that people who have severe paralysis don’t appear to be at higher risk of blood clots. This tells us that something interesting is happening.

“And it turns out that reducing levels of Hsp47 plays a key role in preventing clots, not just in humans, but in other mammals, including bears and pigs.

“When we see something like this in multiple species, that reinforces its importance. Having Hsp47 must have been an evolutionary advantage.”

Hsp47 is released by platelets and is one of the necessary ingredients to enable platelets to prevent and stop bleeding.

When the team analysed the role of the protein in clotting, they found when released into the blood of bears, mice, and humans that it promoted conditions that may give rise to deep vein thrombosis.

They took blood samples from bears in winter, while hibernating, and in summer, while awake and moving around. They also compared people who were immobilised with those who can move and walk, and pigs kept in small pens with pigs that were free to move around in barns.

In all three cases, proteomics experiments showed that the absence of movement was associated with having far less Hsp47.

Professor Gibbins said: “We aren’t totally sure how, but it appears that there is something about movement that keeps Hsp47 at an appropriate level. It could be that the mechanical forces involved in moving around actually have an impact on gene expression, dramatically increasing the amount of Hsp47 that circulates in the blood.

“Now we know that Hsp47 is so important, we can begin to look for new or existing medicines that might be able to inhibit the function of this protein in blood clotting and protect mobile people who are prone to clots.”


Thienel M, Müller-Reif JB, Zhang Z, Ehreiser V, Huth J, Shchurovska K, Kilani B, Schweizer L, Geyer PE, Zwiebel M, Novotny J, Lüsebrink E, Little G, Orban M, Nicolai L, El Nemr S, Titova A, Spannagl M, Kindberg J, Evans AL, Mach O, Vogel M, Tiedt S, Ormanns S, Kessler B, Dueck A, Friebe A, Jørgensen PG, Majzoub-Altweck M, Blutke A, Polzin A, Stark K, Kääb S, Maier D, Gibbins JM, Limper U, Frobert O, Mann M, Massberg S, Petzold T. (2023) “Immobility-associated thromboprotection is conserved across mammalian species from bear to human.” Science, doi: 10.1126/science.abo5044.

Link: https://www.science.org/doi/10.1126/science.abo5044

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