Role of Biochemical and Biophysical Factors on Endothelial-to-Mesenchymal Transformation

Abstract

The prevalence of calcific aortic valve disease is rising and is only treatable by surgical replacement of the stenotic valve. There is currently no biomarker or pharmacological therapy available for the treatment of early aortic valve disease and this is largely due to our limited understanding of the disease mechanisms. One potential mechanism of valve repair and potentially early valve disease is endothelial-to-mesenchymal transformation (EndMT), the initiating event of valvulogenesis. Our preliminary work has shown that extracellular matrix (ECM) composition that mimics diseased valve conditions strongly stimulates mesenchymal transformation. EndMT may be a mechanism for signaling valve interstitial cells toward either valve regeneration or disease and growing evidence indicates that communication between the interstitial cells and the endothelial cells is essential for valve homeostasis. Unfortunately, there is currently no known unifying mechanism of valve disease that connects endothelial cell dysfunction, interstitial cell differentiation, and pathological matrix remodeling. Our research seeks to reveal this mechanism using novel, unique to our laboratory tools, greatly facilitating the discovery and new clinical strategies for controlling early-detected valve disease with minimally invasive interventions.