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AG Thrombozyten und Atherothrombose

(Platelets & Atherothrombosis)

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Blood platelets not only orchestrate hemostasis and are crucially involved in acute coronary syndromes, but have also emerged as modulators of innate immune functions.

 
Platelets and Atherothrombosis

Platelets are classically regarded as ,vessel sealing, cells sensing damaged vessel endothelium and accumulating at the site of vascular injury where they unleash their hemostatic functions in order to stop and control the circulatory leakage. In addition it is now well established that platelets are crucially involved in t he inititiation of atherosclerosis and the functional activity of platelet adhesion receptors is the prerequisite for their interaction with leukocytes and the vessel wall. The functional regulation of platelet adhesion receptors and the pharmacological inhibtion of platelet activation is one of the major topics adressed by our research group.

 

Furthermore platelets have a central role in the coagulation system. The procoagulant surface of activated platelets enables the conversion of central coagulation factors such as factor IX and X to IXa and Xa. These factors trigger the conversion of prothrombin (factor II) to thrombin (factor IIa). Thrombin is a potent activator of platelets and therefore leads to a local amplification of the coagulation cascade by the acivation of additional platelets. Our research group explores the anti-platelet effects of novel anticoagulants in order to develop novel therapeutic athithrombotic strategies that allow a safe and effective combination of anti-platelet and anticoagulant therapies for patients with acute coronary syndromes.

Platelets and Innate Immunity

In the last decade it became evident that platelets are also involved in the initiation of atherosclerosis, inflammation, and angiogenesis through the relase of soluble mediators from intracellular stores and the direct interaction with leukocytes via transmembrane adhesion receptors. Recently, receptors responsible for innate immune response have been identified on platelets. Furthermore, an active role of platelets in innate immune response to pathogens has been described. We and others identified members of the toll like receptor (TLR) family expressed on the surface of platelets including TLR-2, TLR-4 and TLR-9 and observed TLR-specific signaling in platelets. TLRs recognize pathogen associated molecular patterns (PAMPs) and direct innate and adaptive immune responses.

The dissection of the hemostatic and immunological functions of platelets currently respresents a major task in the field and will be the key for the development of platelet targeted therapies acting specifically on platelet mediated innate immune response without affecting platelet hemostatic functions.

Vascular Homeostasis and Progenitor Cells

Vascular inflammation is characterized by a loss of the integrity of the vascular bed. Circulating progenitor cells have the capacity to restore vascular homeostasis via. They adhere to damaged/inflamed endothelium and restore vascular homeostasis via direct interaction with the vessel wall and also in an indirect paracrine manner.


This process is just beginning to be understood. Circulating progenitor cells are a rare population of cells that can be measured and characterized ex vivo from blood peripheral samples. The relative paucity of these cells however is a major hurdle for investigative studies on progenitor cell function and homing processes in the vascular bed. We developed a method to produce high numbers of well defined progenitor cells via an ex vivo expansion and differentiation procedure. This allows the application of pharmacological screening assays and detailed functional studies of the interaction of inflammatory molecules and progenitor cells.

Labor

PD Dr. Ingo Ahrens

Telefon: +49 761 270-70470
Telefax: +49 761 270-70450