HHU StartMedizinische FakultätIRTG 1902PeoplePrincipal InvestigatorsProject 13 - Elvers: Role and Importance of the Extracellular Matrix Protein Biglycan in Platelet Adhesion and Thrombus Formation

Project 13

Cell-cell Communication of platelets, leukocytes and endothelial cells via Pannexin-1

Prof. Dr. rer. nat. Margitta Elvers

Heinrich-Heine-Universität
Department of Vascular Surgery, Experimental Vascular Medicine

Biglycan (BGN) is part of the small leucine-rich proteoglycans and consists of a core protein and one or two side chains which are either chondroitin or dermatan sulfate. Among other functions BGN interacts with different components of the extracellular matrix (ECM) (e.g. collagen, elastin) and is able to modulate the collagen fibrils to increase the stability of the collagen network. After myocardial infarction BGN is needed for tissue remodeling and deficiency of BGN leads to an increased amount of aortic aneurysms. The aim of this project is to determine the role of BGN as an ECM protein in the vessel wall in platelet adhesion and thrombus formation upon injury.

ELISA and qPCR data provide strong evidence that platelets are not a source of BGN. However, we observed increased platelet adhesion under static conditions as well as increased thrombus formation on a collagen-biglycan matrix compared to collagen alone ex vivo. In line with these results we found reduced platelet adhesion at the injured carotid artery in bgn-/0 mice in vivo. Furthermore bgn-/0 mice have a significantly prolonged tail bleeding time as well as significantly prolonged occlusion times of the carotid artery after FeCl3-induced vessel injury. Thus we believe that biglycan in the vessel wall plays an important role in platelet adhesion and subsequent thrombus formation. Accordingly, our results obtained from bone marrow chimeric mice showed that loss of biglycan in the vessel wall is responsible for prolonged bleeding times as well as prolonged occlusion times after injury of the carotid artery in these mice..

In summary our data strongly suggests that biglycan plays an important role in platelet adhesion and thrombus formation upon vessel injury.

 

 

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