Endothelial Cell-specific Loss of Breast Cancer Susceptibility Gene 2 Exacerbates Atherosclerosis
Abstract
Despite mounting concern over the increased risk of cardiovascular disease in breast cancer patients, studies evaluating the common genetic/molecular link between these diseases are limited. Mutations in the breast cancer susceptibility genes (BRCA1&2) predispose carriers to breast and ovarian cancers due to compromised DNA damage repair capacity leading to DNA damage accumulation; in cancer cells, and in other cell-types including endothelial cells, causing atherosclerotic hallmarks of endothelial dysfunction/apoptosis. We present a new understanding of BRCA2’s protective functionality in the setting of atherosclerosis. Studies have thus far demonstrated that while loss of endothelial BRCA2 in mice does not affect a molecular or functional baseline phenotype, endothelial cell-specific loss of BRCA2 exacerbates high-fat diet-induced atherosclerosis in ApoE-/- mice. This study illuminates BRCA2 as a potential therapeutic target in cardiovascular disease and suggests a requirement for studies evaluating the genetic predisposition of BRCA2-mutation carriers for increased risk of atherosclerosis and other cardiovascular diseases.