Potential for fighting dangerous embolism: Researchers have uncovered a mechanism in hibernating bears, other animals and humans that protects against dangerous blood clots during long periods of immobilization. Accordingly, the formation of a special protein involved in blood clotting is down-regulated. The results could lead to the development of new antithrombotic drugs, the scientists say.
Blood coagulation is fundamentally a vital mechanism: in the event of injuries, plugs ensure that body fluids leak out. But the system has a dark side. If the lumps form in the wrong place and then make their way through the vascular system, there is a risk of death. This is exactly the case with venous thromboembolism (VTE), which tops the list of causes of death and harm in humans. Blood clots form in deep veins, for example in the leg. It is already known that problematic functions of immune cells also play a role in this effect. Especially in the lungs, detached blood clots can cause a life-threatening blockage – a so-called pulmonary embolism.
Notes on bears and humans
Certain people have an increased tendency to form venous thromboembolism due to predisposition or illness. A well-known risk factor is also acute immobilization: people who temporarily hardly move due to spontaneous illnesses, operations or injuries have an increased risk of developing dangerous thrombosis. Paradoxically, this only applies for a certain time: people who are chronically paralyzed – for example with spinal cord injuries – no longer have an increased risk of VTE. This suggested that an adjustment effect might be present. Another questioning look in thrombosis research is directed at hibernating bears: Although the animals are sedated for six months, their health is apparently not endangered by venous blood clots.
An international team of researchers has now investigated these indications of a possible protective mechanism. The scientists carried out comparative blood tests: they took samples from Swedish brown bears during hibernation and again in summer when the animals were in their active phase. The researchers also compared blood samples from people who were chronically immobilized to those who were able to move normally. As a further examination system, they used pigs that were kept with severely restricted movement or free-roaming. The team subjected all blood samples to modern examination methods known as proteomics in order to identify possible peculiarities in the blood under the various conditions. The focus was on the characteristics of the blood platelets, which play a crucial role in coagulation.
A platelet protein is downregulated
As the researchers report, one factor in particular turned out to be significant in the comparative studies: “The blood platelet protein with the greatest difference between wintering and active bears was protein 47 (HSP47), which was 55 times higher in the wintering bears was down-regulated,” reports co-author Johannes Müller-Reif from the Max Planck Institute for Biochemistry in Martinsried. The researchers also found a similar pattern in the chronically immobilized humans and in the long-term restricted pigs compared to the controls. The results show that the downregulation of HSP47 during long-term immobilization appears to be a natural adaptive mechanism for thrombosis prevention in various mammalian species.
According to the researchers, the mechanism can also be explained: Apparently, the interaction between the blood platelets and inflammatory cells of the immune system is slowed down by less HSP47, which suppresses the risk of developing venous thrombosis. Further study results also provided indications of how the effect develops: According to this, bed rest in otherwise healthy people led to a significantly reduced HSP47 level with a protective function after about 27 days.
The study results now show considerable potential for medicine, the scientists emphasize: “Now that we know that HSP47 is so important, we can look for new or existing drugs that inhibit the function of this protein in blood clotting and could protect people who are prone to clots,” says co-author Jon Gibbins of the University of Reading.
Source: University of Reading, Ludwig-Maximilians-Universität Munich, specialist article: Science, doi: 10.1126/science.abo5044