Grant: Proof of Principle Program - Phase I

The hardening of arteries (atherosclerosis) is one of the main ways that cardiovascular disease can lead to death. Atherosclerosis starts when the cells lining the inside of blood vessels (endothelial cells) become damaged and the blood vessel loses the ability to expand. Nearly all treatments for atherosclerosis aim at treating the disease in the later stages. There is a growing need to treat the disease in the early stages, to ensure arteries remain flexible to resistant cardiovascular disease. DNAs are blueprints that contain instructions to make sure our bodies function properly. DNA damages can cause cell injury, cell adaptations and cell death. Our objective is to determine if BRCA1, a gene that promotes DNA repair, can help protect endothelial cells and preserve the ability of blood vessels to expand. We will study in-depth the process by which BRCA1 may protect endothelial cells with the specific aim of looking for undiscovered ways in which this protein may help prevent cardiovascular disease. We have made a mouse that does not have the BRCA1 gene in endothelial cells. We will divide these mice (and normal mice) into several groups and compare blood vessel function in mice which have been treated with extra BRCA-1 or nothing. We will also breed these mice with another strain of mice that get atherosclerosis to see if the disease is worse when there is no BRCA-1. The results of this study will let us know if BRCA-1 might help protect against atherosclerosis and may provide a new way by which cardiovascular disease can be prevented.