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Mechanical stress like shear stress caused by high blood flow is one out of many stimuli leading to vascular remodelling in the adult. Shear stress is referred to as the mechanical force induced by the blood flow and acts on the vessel wall surface, whereas wall shear rate describes the deflection of the cell. Shear stress changes with blood flow velocities and represents a physiological stimulus for endothelial cells. Acute elevation of shear stress leads to the production of the vasoactive autacoid nitric oxide (NO). Using this regulatory circuit, the endothelium is enabled to regulate regional blood flow (auto regulation) and pressure without other higher regulatory systems.
In contrast chronically high blood flow (e.g. during physical exercise or by recruitment of collateral vessels after thrombosis) results in an altered expression of certain genes, amongst them we found the endothelial nitric oxide synthase (eNOS). We showed that this induction of gene expression is dependent on specific cells matrix interactions via non-integrin matrix receptors indicating an important regulatory role of the cell-matrix-interaction in mechano-sensitive signalling cascades.
It is also observed that upon persistent high blood flow the vessel wall is remodelled reflecting a vascular adaptation to enhanced mechanical demands in order to maintain a proper functionality. In the context we are further interested in identifying specific key mediators of induction and progression of those remodelling processes. Recently, we have identified a new proteolytic activity, which is found to be up regulated upon shear stress. Moreover, we found that this activity is necessary for the shear stress dependent release of the angiogenic growth factor FGF-2 whose release mechanism has not been fully understood yet. Additionally, using inhibitors we could show that the FGF-2 release critically depends on the engagement of certain integrins.
Dr. Torsten Gloe
Phone: +49 (0)621/383-71516