Poster abstracts
Poster number 52 submitted by Matt VandeKopple
A novel role for Scleraxis in promoting valve interstitial cell quiescence
Matt VandeKopple (Molecular, Cellular, and Developmental Biology, The Ohio State University), Joy Lincoln (Center for Cardiovascular and Pulmonary Research, The Research Institute at Nationwide Childrens Hospital)
Abstract:
Heart valve disease affects 2.5% of the general population yet little is known about the
pathophysiology and current therapies remain limited. In healthy valves, function is achieved by
neatly stratified layers of extracellular matrix (ECM) that provide all the necessary
biomechanical properties throughout life. ECM secretion and organization is established during
development and mediated by embryonic activated valve interstitial cells (EaVICs). These
precursor cells mimic myofibroblasts and express high levels of α-smooth muscle actin (SMA).
After birth, EaVICs undergo quiescence, lose SMA expression and serve to maintain valve
homeostasis in the absence of disease. However, in response to pathological stimuli quiescent
VICs become activated and promote pathological ECM remodeling leading to compromised
biomechanical function. Therefore it is imperative that VIC quiescence is maintained to prevent
disease processes. Despite this, regulators of this process have yet to be identified. Here we
use in vivo and in vitro assays to show that the bHLH transcription factor Scleraxis (Scx) is
required for VIC quiescence after birth, as loss of function leads to prolonged expression of
activated VIC markers including SMA and Periostin. Ongoing studies are utilizing a new
transgenic model to determine if Scx is sufficient to prevent VIC activation and valve disease in
a genetically susceptible mouse model. Overall, these studies suggest that Scx is a novel
regulator of VIC phenotypes, thereby providing insights into mechanistic-based therapies in the
prevention and treatment of valve disease.
Keywords: Heart Valve, Scleraxis, Myofibroblast