Venous thrombi originate in the valve pocket of the deep veins, in a milieu that is characterized by intermittent hypoxia and vortex flow (stasis). To study the involvement of hypoxia in the pathogenesis of VTE, we will characterize endothelial cells and monocytes responses to sustained and intermitted (pulsatile) hypoxia by multi-color flow cytometry and RNA seq. We aim to identify hypoxia-induced proteins that are causally related to VTE and to unravel novel mechanisms for the initiation of disease. For this, we will identify hypoxia-induced proteins from a whole transcriptome analysis of hypoxic endothelial cells and monocytes. The association between hypoxia induced proteins and VTE will be investigated in a case-cohort study. Protein quantitative loci analysis and Mendelian Randomization will be performed to reveal potential causal relationships, and the prothrombotic potential of the proteins will be tested in in vitro experiments.
Principal Investigator: John-Bjarne Hansen
External collaborators: Therese H. Nøst, Kristian Hveem (HUNT Center for Clinical and Molecular Epidemiology, NTNU)
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