Herm-Jan (H. J.) Brinkman PhD
analytical chemistry and biochemistry
Endothelial cells, their procoagulant side
Promotor: Prof. Dr. K. Mertens (Sanquin Research and Faculty of Pharmaceutical Sciences, University of Utrecht).
Co-promotor: Dr. J.A. van Mourik (Sanquin Research)
10 November 2004 - University of Utrecht
Role of endothelial cells in the regulation of the haemostatic process.
Endothelial cells line the vessel wall and are in direct contact with the blood. Upon vessel trauma, blood platelets adhere to sub-endothelial tissue at the site of injury and aggregate and localized generation thrombin ensures tightening of the thrombus by the formation of a fibrin network. Endothelial cells are not bystanders in the haemostatic process. They are actively involved in maintaining the fluidity of blood and do not solely shield blood constituents from the sub-endothelial tissue. Endothelial cells e.g., synthesize and release components that inhibit platelet aggregation and thrombin formation. Opposing these antithrombotic and anticoagulant properties, endothelial cells also synthesize and release components that are essential for platelet adhesion and aggregation. Furthermore, the endothelial cell membrane mediates the generation of thrombin, a process for long attributed solely to the adhered and aggregated platelet. This intriguing haemostatic paradox of the endothelial cell is challenging and far from understood.
- Protein chemistry
- Cell biology
- Isolation of blood platelets and isolation and culturing of vascular cells
- Platelet aggregation and adhesion measurements
- Analysis of clotting factors and clotting factor related proteins
- Measurement of coagulation reactions in model systems employing purified coagulation factors as well as measurements in plasma, in the absence and presence of vascular cells and platelets.
Herm-Jan started as a technician at the department of Blood Coagulation at the Central Laboratory of Blood Transfusion Service (now Sanquin PDR). Initially he worked on fatty acid metabolism of vascular cells, cooperated in research on the glycoprotein composition of the endothelial cell membrane and participated in several other studies related to endothelial cells and von Willebrand factor. Subsequently, he moved to the field of regulation of the coagulation process and studied the role of endothelial cells in the activation of clotting factor X by factor VIIIa/IXa complexes and did research on the proteolytic inactivation of protein S, a natural anticoagulant. He accomplished his PhD thesis when working on the last two subjects.