Poster abstracts
Poster number 48 submitted by Lindsey J. Miller
Exploring endothelial cell dynamics in the development, maintenance and regeneration of heart valves
Lindsey J. Miller (Department of Pediatrics, The Ohio State University, Columbus, OH, USA;The Research Institute at Nationwide Childrens Hospital Department of Pediatrics, The Ohio State University, Columbus, OH, USA), Blair F. Austin (Center for Cardiovascular and Pulmonary Research, The Research Institute at Nationwide Childrens Hospital), Joy Lincoln (Department of Pediatrics, The Ohio State University, Columbus, OH, USA;The Research Institute at Nationwide Childrens Hospital Department of Pediatrics, The Ohio State University, Columbus, OH, USA)
Abstract:
Heart valve insufficiency affects ~2.5% of the population with increasing incidence in the elderly. Studies have shown that valve dysfunction is caused by changes in the contribution and organization of extracellular matrix (ECM) that lead to biomechanical failure. Deposition and degradation of the ECM is mediated by valve interstitial cells (VICs) and data suggest that overlying valve endothelial cells (VECs) establish and maintain function of the VIC population. Therefore, we hypothesize that changes in endothelial cell dynamics underlie valve dysfunction. To address this, we developed a method to isolate VECs from Tie2-GFP mice using FACS analysis. With this approach we performed RNA-seq on VECs isolated from embryonic (E14.5), post-natal (PN), adult (4 months) and aged (15 months) mice and generated unique molecular profiles at each time point. Pathway analyses revealed VECs during embryonic and post-natal growth are highly proliferative and express pluripotency markers including telomerase (Tert) compared to adult VECs. However, although mRNA expression decreases, Tert activity remains high in adult stages. As it is unclear whether this pluripotent subpopulation is resident to the valve or arises from a satellite source, we are examining the contribution of bone marrow-derived (BM) progenitor cells to the valve and have data to show that BM cells incorporate into the VEC layer of adult mice. Ongoing studies will examine BM contribution to VECs in mice exposed to valve injury or disease. Together these results highlight the pluripotent potential of VECs after birth and will provide insight into the therapeutic potential of VECs for heart valve regeneration and repair.
Keywords: Heart valve, endothelial cell, regeneration