Status: 04/13/2023 8:00 p.m
When people are bedridden for a long time, the risk of thrombosis increases. Brown bears are different: they can sleep for months without any risk of falling ill. Why is that? The answer to this question could open up new therapeutic options.
It is estimated that one in 1,000 adults in Germany develops a thrombosis every year – a blood clot that impedes the blood supply and, in extreme cases, completely blocks the vein. The possible consequences, such as a pulmonary embolism or a stroke, can be life-threatening.
Thrombosis is often caused by immobility – i.e. sitting or lying down for a long time. But why can brown bears sleep almost motionless for months in winter without coming close to the risk of this disease? And why do paraplegic patients not have an increased risk of thrombosis after the acute phase of the injury?
An international team of researchers led by Tobias Petzold from the LMU Klinikum in Munich investigated these questions.
Bears form natural defense mechanisms
The scientists found out that brown bears and paraplegics use a mechanism that reduces the interaction between blood platelets and immune cells and thus prevents the formation of blood clots.
“For us as researchers, it’s always fascinating when you learn something more about your own human organism – how it works and what happens in it,” said Petzold in an interview with the daily News. The team also hopes that the results, which have now been published in the scientific journal “Science”, will lead to new therapy options.
Tobias Petzold, cardiologist LMU Klinikum Munich, on the protective mechanisms of brown bears against thrombosis
4/13/2023 3:21 p.m
Blood collection in Sweden
The research project began with two trips to central Sweden for the heart and circulatory system specialists at the LMU Klinikum led by researcher Petzold – one in summer and one in winter. A whole flock of brown bears has been scientifically examined there for more than ten years.
The animals carry GPS tags that mark their whereabouts, were stunned for a blood draw, and then released back into the wild. Cardiologist Petzold and his colleagues analyzed the samples in a mobile laboratory – in particular with regard to the question: Does the coagulation system of brown bears differ during hibernation and during summer activity? The so-called plasmatic coagulation system normally plays a crucial role in the development of venous thrombosis. “But we didn’t find any dramatic, relevant difference,” says cardiologist Manuela Thienel, co-first author of the study.
In Sweden, brown bears have been scientifically studied for years, where the research team took blood samples.
Image: picture alliance / TT NEWS AGENC
Further investigations in Munich
The researchers took some of the blood samples with them to Munich, where they examined the blood platelets more closely in their laboratories. It turned out that in the hibernating brown bear’s body, “the interaction between the blood platelets and the inflammatory cells of the immune system is slowed down,” says cardiologist Petzold, “that explains the absence of venous thrombosis.”
The scientists then demonstrated exactly the same mechanisms in paraplegic patients – and in healthy subjects who literally lay in bed for three weeks as part of a test by the European-German and US space agencies (DLR and NASA).
Nearly 2700 active proteins quantified
To uncover the molecular mechanism behind the protective process, almost 2,700 active proteins in the bears’ blood platelets were then quantified. Crucial here: During hibernation, 71 proteins were up-regulated and 80 down-regulated compared to summer activity. “The platelet protein with the greatest difference between hibernating and active bears was heat shock protein 47, which was downregulated 55-fold in the hibernating bears,” explains Johannes Müller-Reif from the Max Planck Institute for Biochemistry in Martinsried.
The researchers were able to show that the downregulation of this HSP47 occurs during long-term immobilization in various mammalian species and is therefore an evolutionarily conserved mechanism for thrombosis prevention.
Hope: drug that prevents blood clots
Low HSP47 protein levels reduce the interaction of blood platelets and inflammatory cells. In fact, according to Petzold, “HSP47 alone is able to activate the inflammatory cells”. Conversely, in biomedical terms, this means that if the HSP47 could be blocked with a suitable molecule in immobilized acute patients, the risk of venous thrombosis could possibly be prevented.
In this regard, we are still at the beginning, emphasizes Petzold – but: “One of our dreams would be to develop a drug that can ideally also be administered as a tablet – and that binds to the blood cells of the patient and blocks certain proteins, to prevent the formation of blood clots,” says Petzold.