Vascular smooth muscle cells - friend or foe in vascular disease?

Mechanotransduction (transmission of biomechanical forces into cellular signals) in vascular smooth muscle is crucial for adaptation to elevated blood pressure.

Our hypothesis is that defective mechanotransduction result in excessive tensile stress and pathological changes in the vascular wall.

The aim of the present project is to identify a novel mechanism for vascular adaptation to mechanical stress involving the transcriptional regulators YAP/TAZ, and to understand their role in vascular disease.

Furthermore, the project aims to clarify how excessive mechanical force promotes inflammatory vascular disease and how this can be prevented using novel therapeutic approaches.The aims are addressed using unique smooth muscle specific and inducible YAP and/or TAZ KO mice, miR-143/145 KO mice, human arteries in organ culture and isolated human smooth muscle cells.

Smooth muscle mechanotransduction and contractile function is tested using wire- and pressure- myography and organ culture models.

The mice are subjected to vascular disease models in vivo and the therapeutic potential of novel galectin-3 inhibitors is evaluated in collaboration with Galecto Inc.In summary, our hypothesis is that smooth muscle cells can both protect and contribute to vascular disease by adaptation or maladaptation to mechanical forces.

This project will reveal novel mechanisms involved in vascular mechanotransduction and identify therapeutic targets that can be used to treat vascular disease in humans.