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Biological rhythm with a significant influence on arterial calcification
Arterial calcification is a very common complaint that can have fatal consequences in the worst case. The changes in the blood vessels are subject to fluctuations in the time of day, scientists from the Ludwig Maximilians University Munich (LMU) report. In a recent study, the researchers found that the so-called circadian rhythm has a significant impact on atherosclerosis.
According to the researchers, the biological rhythm influences the extent of the deposits on the vessel walls, although this could also be used for therapeutic purposes. Treatment could therefore focus on the times of the day when a particularly large amount of deposits are formed. According to the researchers, this would enable decisive improvements in the therapeutic approaches. The researchers published their study results in the journal "Cell Metabolism".
How does the biorhythm affect the hardening of the arteries?
For the first time, the team headed by Professor Oliver Söhnlein from the Institute for Prophylaxis and Epidemiology of Circulatory Diseases at the LMU was able to demonstrate in his current study what influence the biological rhythm has on atherosclerosis. This internal clock controls all vital functions in the body, from body temperature to blood pressure to the release of certain enzymes that are subject to daily rhythm fluctuations, the scientists explain. The circadian rhythm also has a significant influence on the vascular disease atherosclerosis. The symptom is commonly known as hardening of the arteries and can ultimately lead to a heart attack or stroke.
Molecular mechanisms examined
The scientists examined the molecular mechanisms in atherosclerosis that lead to deposits in the inner wall of the arteries. Here, cells of the immune system migrate from the blood to the damaged area and attract more and more cells via signal substances until the immune response finally derails, the experts explain. This atherosclerotic inflammation develops over years, but the recruitment of the cells is subject to daily rhythm fluctuations. The researchers have now been able to demonstrate such fluctuations in the mouse model.
Time shift in leukocyte activity
"At certain times of the day, three times as many leukocytes are on the way to the inflammation site as usual," reports Prof. Söhnlein of the test results. However, their rhythm was shifted by about twelve hours compared to their occurrence in the microcirculation in the veins. According to the researchers, this shift between the two vascular systems is interesting from a therapeutic point of view. Because the recruitment of white blood cells in the microcirculation is important in acute infections such as blood poisoning, which is why ideally the recruitment of the immune cells in the microcirculation should be maintained while it is stopped in atherosclerotic inflammation.
Can arterial calcification be stopped?
In their investigations, the scientists not only identified the molecular mechanism that can be used to stop the recruitment of leukocytes, but have already successfully tested it. Blocking the CCL2 enzyme prevented it from sending out signals that would cause additional leukocytes, the researchers report. By taking into account the daily rhythmic fluctuations, it was also possible to stop recruiting only at the atherosclerotic inflammation sites, while the microcirculation was not impaired.
Further investigations planned
"Our study shows how circadian patterns can be used for timed therapeutic intervention," emphasizes Prof. Söhnlein. In further studies, it must now be clarified to what extent circadian rhythms contribute to the destabilization in advanced atherosclerosis. The researchers are also increasingly planning to investigate the circadian regulation of processes in the atherosclerotic deposit itself, such as the question of whether cell death is controlled in a circadian manner. (fp)