Dr. Stephanie Lehoux

1. Atheroprotective role of Semaphorin 3a: Semaphorin 3a (Sema3a) was initially identified as a secreted neurorepellant, but recent evidence points to its potentially important modulatory role in inflammation. Remarkably, the effects of Sema3a on macrophages, the most abundant cells in the atherosclerotic plaque, have never been investigated. This project aims to verify whether Sema3a can curb the atherosclerotic process by promoting macrophage motility and by enhancing the clearance of apoptotic cells through phagocytosis, using in vitro and in vivo models.
2. Study of plaque regression pocesses using a unique AVF model: Clinical studies indicate that atherosclerotic regression is a realistic goal in patients, and it can be achieved through increased shear stress. We have devised a model whereby atherosclerotic plaques in the brachiocephalic artery (BCA) of mice regress when exposed to high blood flow due to the creation of an arteriovenous fistula (AVF). This project will define the mechanisms whereby plaque reversal occurs, investigating the changes in plaque composition incurred, the role of matrix metalloproteinases, and the contribution of immune cell subsets.