Poster abstracts

Poster number 51 submitted by Lindsey J. Miller

Molecular and phenotypic characterization of valve endothelial cells during development

Lindsey J. Miller (Molecular, Cellular, and Developmental Biology Graduate Program, The Ohio State University, Columbus, OH, USA), Joy Lincoln (Center for Cardiovascular and Pulmonary Research, The Research Institute at Nationwide Childrens Hospital, Columbus, OH, USA. Department of Pediatrics, The Ohio State University, Columbus, OH, USA.)

Abstract:
Normal valve structure consists of stratified layers of extracellular matrix (ECM) interspersed with valve interstitial cells (VICs) surrounded by a monolayer of valve endothelial cells (VEC)(1). VECs serve to sense the hemodynamic environment and communicate with underlying VICs to regulate valve integrity, which is essential for both valve development and maintenance. In contrast, diseased valves are characterized by disorganized ECM, VIC disarray, and disruption of the VEC monolayer; suggesting VEC dysfunction may be an underlying cause of valve disease (2, 3). Although disease pathology has been defined, the underlying molecular mechanisms are largely unknown; however, studies suggest that disease manifested later in life has origins in embryonic development. Despite their importance, the molecular phenotypes of VECs have not been explored. Therefore, the goal of this study is to determine the differential gene expression profile of VECs during hallmark stages of valve development and in models of valve disease. To do this, we have developed a novel method to isolate VECs from embryonic, post natal, and adult mice. Using this method, VECs will be isolated at embryonic day (E)14.5, post natal (PN) and adult (4 month old) stages from Tie2GFP reporter mice and subjected to RNA-seq analysis to generate an expression profile of healthy VECs over time. In addition, profiles of VECs from mouse models of disease will be generated to define molecular differences in VECs between healthy and diseased valves. Generation of these expression profiles will provide important insights into the molecular function(s) of VECs in developing and mature valves, and identify potential mechanisms and novel candidate genes underlying valve disease.

References:
1. Tao G, Kotick JD, Lincoln J. Heart valve development, maintenance, and disease: The role of endothelial cells. Current topics in developmental biology. 2012;100:203-232
2. Weinberg EJ, Mack PJ, Schoen FJ, Garcia-Cardena G, Kaazempur Mofrad MR. Hemodynamic environments from opposing sides of human aortic valve leaflets evoke distinct endothelial phenotypes in vitro. Cardiovasc Eng. 2010;10:5-11
3. Hinton RB, Jr., Lincoln J, Deutsch GH, Osinska H, Manning PB, Benson DW, Yutzey KE. Extracellular matrix remodeling and organization in developing and diseased aortic valves. Circulation research. 2006;98:1431-1438

Keywords: valve endothelial cells, heart valve, RNA-seq