Identification of signaling pathways as druggable targets to combat vascular stiffness, a life threatening vascular pathology with high impact on multiple organs.

Vascular stiffening is a growing epidemic associated with a high risk of cardiovascular disease, and end organ-damage in kidney and brain. No effective therapies to combat this life threatening vascular pathology currently exist, which is largely due to the lack of knowledge on the underlying molecular mechanisms. Therefore, this project aims to identify novel druggable targets which opens up new perspectives for discovery and evaluation of inventive therapies. Endothelial dysfunction and vascular calcification are well known pathological processes leading to vascular stiffness. Established mouse models of endothelial dysfunction and vascular calcification will therefore be used to identify the molecular signaling pathways responsible for vascular stiffness by means of a proteomic approach of arterial tissue. Additionally, we will explore the reciprocal relationship between endothelial dysfunction, vascular calcification and stiffness. As impaired autophagy has been suggested to play a role in vascular aging, this project will also focus on its role in vascular calcification and stiffness. To explore whether autophagy is a candidate target for future intervention studies, complementary in vivo studies will be performed that investigate the effect of both autophagy induction and defective autophagy on vascular calcification and stiffness. Broader ambitions of this project are to reduce the impact and lower the economic burden of vascular stiffness on society.

Keywords:EXPERIMENTAL STUDY, MOUSE MODELS

Disciplines:Systems biology