Characterisation of BRCA1 as a novel epigenetic target for diet intervention with blueberry flavonoids to improve endothelial dysfunction and to prevent cardiometabolic health.

According to the world health organization, cardiovascular diseases account for the highest mortality numbers with approximately 30% of all deaths worldwide. Atherosclerosis is a chronic inflammatory condition associated with endothelial dysfunction and phenotypic changes in smooth muscle cells and leukocytes, playing early and permissive roles in the development, progression, and clinical course of the disease. These dramatic changes in cell phenotypes are accompanied by changes in gene expression and epigenetic marks. Interestingly, we and others identified reactivation of BRCA1 expression as a novel strategy to prevent or to attenuate atherosclerosis progression. In this proposal we want to further characterize the role of BRCA1 in leukocyteendothelial cell functions in cardiometabolic health. Furthermore, we will evaluate the efficacy of cardioprotective blueberry flavonoids to restore BRCA1 expression by epigenetic reactivation in experimental models in vitro and in human diet intervention studies. From an epidemiological point of view, these results provide important clues regarding a potential susceptibility of silenced BRCA1 epitypes to cardiometabolic disease, in addition to the well-documented predisposition towards cancer syndromes