New junior research group investigates how the immune system reacts to stress and could thus damage heart health

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Stress ensured survival in evolutionary terms. But what was once life-saving could now be life-threatening. When Stone Age humans suffered an injury, such as a bite from a saber-toothed tiger, their immune system kicked in and their bodies formed useful small blood clots (microthrombi) to trap pathogens. Stress hormones such as adrenaline may have helped in this process.

Today, as head of a new DZHK junior research group, Dr. Kami Pekayvaz is investigating whether and how stress in modern humans promotes thrombosis, i.e., harmful blood clots—and thus cardiovascular diseases such as heart attacks, strokes, or pulmonary embolisms.

The young doctor treats patients at Munich's LMU Hospital while also conducting research. "I often see patients here with heart attacks or other thrombotic diseases who have been under acute stress, for example due to psychological strain. We know that stress and the associated hormones such as adrenaline increase the risk of such diseases. However, it is still unclear exactly how these hormones affect the immune system and thus promote thrombosis. Now I have the opportunity to scientifically investigate the experience I have gained in my daily clinical work with my junior research group," says Pekayvaz. The DZHK is funding the junior research group to investigate the adrenaline-neutrophil axis with €1.65 million over the next six years.

Better understanding the role of the immune system in cardiovascular disease

Neutrophils are important defense cells of the immune system that respond quickly to infections, sterile inflammation, or environmental stress. At the same time, the body releases acute stress hormones such as adrenaline—collectively referred to as catecholamines in technical terminology.

"A catecholamine-neutrophil axis could be evolutionarily significant in containing bacterial infections by means of thrombi in small vessels. On the other hand, under modern environmental stress, it could also cause harmful blood clots in large vessels, i.e., macrovascular thrombosis," says Pekayvaz. "This project offers the opportunity to better understand the role of the interaction between stress hormones and the immune system in thrombotic cardiovascular diseases," explains the researcher.

Kami Pekayvaz completed his medical studies in Munich with stays at the University of Oxford, among other places. He wrote his doctoral thesis on atherosclerosis and has been conducting research at LMU Hospital for years on the interface between inflammation and cardiovascular diseases using the latest translational analysis methods.

Bridge between laboratory and clinic

"We are looking at what happens when neutrophils and adrenaline come together in vitro and in vivo – that is, in test tubes and in animal models. And we are looking at what happens when neutrophils cannot respond to adrenaline because we block the receptors for these stress hormones," explains Pekayvaz. "We are interested in how harmful vascular occlusions, i.e., venous or arterial thromboses, develop under these conditions. And what consequences this has for bacterial sepsis, in which the immune system uses microthrombi to contain pathogens."

To this end, Pekayvaz and his team of physicians, biologists, and bioinformaticians at LMU Hospital are utilizing state-of-the-art techniques in single-cell analysis and microscopy, as well as newly developed genetic mouse models. They analyze blood samples from patients with heart disease, thereby building a bridge between the laboratory and the clinic.