Biomechanical mechanisms that control endothelial repair and function in stented arteries.

Stent deployment following balloon angioplasty is used routinely to treat coronary artery disease. These interventions cause damage and loss of endothelial cells, which can promote in-stent thrombosis and restenosis. Injured arteries are repaired by locally-derived
endothelial cells and by circulating endothelial progenitor cells which migrate and proliferate to re-populate denuded regions. However, the molecular and biomechanical mechanisms that control endothelial cell repair and function in stented arteries are poorly understood. We hypothesize that stents modify endothelial repair processes, in part, by altering fluid shear stress, a mechanical force that has multiple effects on endothelial physiology.

The PhD Studentship will couple cell and molecular approaches to imaging and computational fluid dynamics to identify pro-migratory signalling pathways that are dysregulated by abnormal shear stress in stented coronary arteries. The study, which will
be performed using in vitro flow cells and a porcine model of percutaneous coronary intervention coupled to intravascular imaging, will illuminate the fundamental biomechanical processes that govern endothelial cell repair and may inform the development of novel therapies to promote re-endothelialisation in stented arteries.