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TRP X12 Vascular Inflammation and Dysfunction

Funding period: 01.09.2015 – 31.08.2019

Project Summary

Arterial hypertension is the most relevant risk factor for death and morbidity worldwide. We aim to elucidate the mechanisms of cooperation of different coagulation factors on myelomonocytic cells interacting with platelets driving vascular inflammation and high blood pressure. To study myelomonocytic-specific effects, we will crossbreed special mouse strains to obtain mice that specifically lack single coagulation factors in myelomonocytic cells (“conditional knockouts”). The platelet interaction with leukocytes will be studied further with CD11b-/- mice and mice lacking certain receptors of the Apolipoprotein family. Arterial hypertension will be induced by infusion of angiotensin II for 7 days via osmotic minipumps in these genetically altered mice compared to wild type controls. Endpoints will be assessed by invasive and non-invasive blood pressure recording and by intravital microscopy, relaxation studies, flow cytometry analysis and protein/mRNA expression studies of arterial vessels. In a translational approach, we will study alterations of the distinct platelet glycoprotein receptor and coagulation factor pathways and of SNPs in their genetic networks with help of the CTH biobank. We expect, that inhibition of certain coagulation factors on myelomonocytic cells will protect from vascular injury leading to hypertension. Interference in these pathways will attenuate formation of thrombin, a coagulation factor and protease which is intimately involved in vascular dysfunction, in the platelet-leukocyte-vessel-wall microenvironment. Identification these mechanisms will serve as the foundation to develop novel therapeutic approaches to treat cardiovascular disease.

Principle Investigator

Prof. Dr. Med Philip Wenzel, MD
Prof. Dr. Med Philip Wenzel, MD

Deputy director Cardiology I, DZHK Principal Investigator

06131 17-7695