Grant: Project Grant

In Canada, as in most developed countries, atherosclerosis is one of the leading causes of illness and death. According to the most recent data, one in five deaths in Canada is due to atherosclerosis-associated cardiovascular complication. Despite great medical advances, therapies are urgently needed to improve the cardiovascular function in atherosclerosis. Endothelial cells, which line the innermost layer of blood vessels, play important roles in maintaining blood vessel function, thereby understanding the mechanisms underlying abnormal endothelial function may serve to uncover novel therapeutic approaches to treat atherosclerosis and associated cardiovascular dysfunctions. DNA is the genetic material present in every cell type, and is prone to damage by various stressors. BRCA2 is a protein molecule, which maintains the DNA integrity by repairing the damaged DNA. Loss of BRCA2 function causes breast and ovarian cancer. DNA damage not only causes cancer but also plays important role in the development of cardiovascular diseases. Our aim is to understand if loss of endothelial BRCA2 results in increased endothelial cell death, endothelial dysfunction and if it also promotes atherosclerosis-associated cardiovascular diseases. In this proposal, we will use an animal model of atherosclerosis. This animal model will also lack BRCA2 in their endothelial cells. We want to investigate if there will be increased atherosclerosis-associated endothelial dysfunction and endothelial cell death after feeding these animals with high fat diet. Our study will delineate a new role of BRCA2 in atherosclerosis, which may help identifying a potentially new therapeutic target to treat cardiovascular diseases. Our study may point to an increased possibility of developing cardiovascular diseases in breast and ovarian cancer patients with mutation in BRCA2 gene.