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Arbeitsgruppe Platelets in Cardiometabolic Disease

Leitung: Dr. rer. nat. Nancy Schanze

Research focus

My research group is interested in the role of platelets in the development and progression of cardiometabolic disease. We look at the platelet in its role as a multifaceted modulator of inflammation and angiogenesis apart from its classical role in hemostasis. Our aim is to elucidate how platelets influence different cell types, such as endothelial cells, leukocytes, cardiomyocytes or adipocytes, thereby modulating the course of disease. With the help of mouse models, cell culture techniques and clinical samples we want to unravel fundamental mechanisms that lead to the discovery of therapeutic targets and biomarkers.

Platelets

Platelets are anucleate cells that play a primary role in hemostasis. But platelets have also been recognized as potent modulators of inflammation and angiogenesis. For example, platelets secrete chemokines like RANTES, serotonin or platelet factor 4 (PF4) at sites of inflammation to recruit leukocytes. To establish direct cell-cell interactions with leukocytes or endothelial cells, platelets can secrete or expose adhesion proteins such as P-selectin, fibronectin, fibrinogen or von Willebrand factor. Furthermore, platelets can activate the complement system and are even able to directly capture and neutralize pathogens. Several pro-angiogenic (e.g., stromal cell-derived factor-1α) and antiangiogenic factors (e.g., PF4) are stored in distinct subpopulations of platelet α-granula from where they are released differentially in response to specific agonists. An interplay between platelets and the complement system in angiogenesis was recently shown.

Cardiometabolic disease

Cardiometabolic disease is a spectrum of common conditions including CVD, diabetes, insulin resistance and non-alcoholic fatty liver disease. Globally, the number of people experiencing one or more of these diseases during their lifetime is increasing. Myocardial infarction, diabetes mellitus and stroke are among the leading causes of mortality. Chronic inflammation in humans is associated with accelerated development of cardiometabolic diseases. The mechanisms that connect inflammation, e.g., in obesity, with the development of metabolic and cardiovascular complications are complex and not completely understood. Adipose tissue inflammation that leads to the development of the metabolic syndrome is driven by several immune cells, especially macrophages and T-cells. However, a role of platelets has not been sufficiently studied in this context.