Investigations into Semaphorin signaling and Furin as novel effectors of coronary artery disease

Coronary Artery Disease (CAD), one of the most common heart disease, is the leading cause of death in the world. One of the main causes for CAD is atherosclerosis. There have been many studies done to identify genes responsible for atherosclerotic plaques formation. Recently, Genome-wide association studies (GWAS) done by Ghosh et al. has shown a strong association between semaphorin pathway with CAD. Additionally, the protease Furin was found to be a member in 6 of the 32 replicated, CAD associated pathways. To follow up for these novel findings, present studies examined the regulation of Semaphorin pathway gene expression and the effects of Furin knock-down in RAW264.7 macrophages. CAD characterized cells were induced using human high OxLDL and Furin knock-down was carried out using siRNA. Preliminary results suggest that Semaphorin pathway could be regulated by OxLDL with decrease in NRP1 and PLXNA2 expression. Presence of OxLDL also reduced the expression of Sma and Icam1 by more than 50%. Knock-down of Furin reduced expression of IL-1B, CD86 and CD205 by more than 50%. Future studies will include measurement of protein levels for candidate gene and examine of OxLDL and Furin knock-down effect in endothelial and vascular smooth muscle cells. Doctor of Philosophy (SBS)