Investigating the role of the bone morphogenetic proteins in the development of atherosclerosis. (360G-Wellcome-099824_Z_12_A)

Atherosclerosis, a major cause of cardiovascular disease, affects millions of people every year. Atherosclerosis is characterised by vascular inflammation, lipi deposition and calcification in arterial walls. Evidence has shown that bone morphogenetic proteins (BMPs) are involved in thedevelopment of atherosclerosis. For example enhanced BMP2 activity has been implicated in triggering pro-inflammatory effects on the endothelium by accelerating vascular calcification. Although BMPs have been shown to promote atherosclerosis, paradoxically, reduced expression of the bone morphogenetic protein receptor-II (BMPR-II) has been shown to induce inflammation of the endothelium both in vitro and in vivo. The hypothesis underpinning this research project is that BMP signalling is involved in atherosclerosis. However, the mechanisms by which specific BMP ligands and their receptors contribute to or protect from disease, and the cell-specific nature of these responses remain unknown. The key goals of this study are: o To determine the effects of BMP ligands on the interaction between monocytesand endothelial cells. o To characterise BMP signalling in a mouse model of atherosclerosis. o To investigate the cell specific nature of the BMP signalling in atherosclerosis using a conditional knock-in mouse. o To apply the knowledge gained from investigating the aforementioned scientific questions with the view to intervene therapeutically.