Joan Fernandez Esmerats
PhD Proposal Presentation
Date: October 26th, 2016
Time: 2-4 PM
Location: HSRB E-182 (Emory University)
 
Committee:
Hanjoong Jo, PhD (Advisor)
Robert M. Nerem, PhD
Ajit Yoganatahn, PhD
Andres J. Garcia, PhD
Vinod H. Thourani, MD

Title:  Shear stress-sensitive microRNA-483-3p regulates aortic valve endothelial dysfunction and calcification

Abstract:
Calcific aortic valve disease (CAVD) is a significant cause of elderly morbidity and a risk factor for additional cardiovascular events. There is a lack of non-invasive therapeutics due to an incomplete understanding of the pathophysiological mechanisms underlying CAVD. The fibrosa layer facing the aorta preferentially calcifies and experiences low magnitude and oscillatory shear stress (OS). The ventricularis layer facing the ventricle experiences a high-magnitude and pulsatile, unidirectional shear stress (LS) and rarely calcifies. However, the molecular mechanisms governing side-specific CAVD are unknown. This work aims to understand these molecular mechanisms by studying the role of miRNA-483, a side and shear-specific miRNA, which was identified using microarray analysis and, to develop a targeted-delivery method using nanoparticles to treat CAVD. We hypothesize that loss of miR-483 in the fibrosa leads to calcification and by preferentially delivering miR-483 we can inhibit side-specific CAVD. To test this hypothesis, we propose following aims: 1) Test the role of miR-483 in CAVD, 2) Determine targets of miR-483 that regulate CAVD and 3) Assess whether pBAE nanoparticles can side-specifically target the fibrosa layer. Completion of this work could provide novel therapeutic targets as well as a novel side-specific delivery method to treat CAVD.