Grant: CIHR Fellowship

Cardiovascular disease (CVD) mortality has declined over the past 50 years due to improvements in drug therapy and disease management, most notably in lipid-lowering therapy. Despite patients meeting lipid-lowering goals, CVD remains a leading cause of death. Therefore, identifying molecular mechanisms that regulate CVD progression may provide insight into how to further mitigate disease risk. Cells within the fatty plaques on artery walls are under conditions of stress. Cells respond to changes in conditions and stress by forming complexes called RNA granules, comprised of RNA and protein, that coordinate the cells response. Although these complexes have been observed in cells within fatty plaques, there exact role and which molecular events they coordinate in CVD is uncharacterized. The proposed project will investigate the role of two RNA granules, stress granules and processing bodies, in two different cell types in CVD, the smooth muscle cell and macrophage. In my first aim, I plan to establish the techniques required to study these granules in macrophages and smooth muscle cells. In my final aim, I plan to take these findings and extend them to a mouse model of CVD. Understanding the role of RNA granule formation in the context of CVD could provide novel molecular insight into CVD development and could identify potential therapeutic targets.