BRITE Relaunch: Biomechanics and Mechanobiology of Venous Valve Degeneration

About This Grant

Chronic venous insufficiency is a vascular disease in which damage to leg veins due to high blood pressure reduces efficient blood flow back to the heart. Currently, understanding of the mechanical and biological processes responsible for venous valve damage is limited. This BRITE Relaunch project aims to provide the first data on how the cells of the venous valves respond to mechanical forces associated with high blood pressure and tissue damage. In addition, the research seeks to develop computer models to simulate these processes at the tissue and cellular levels. This work will add to fundamental knowledge and looks to broadly impact the design of replacement valves, on heart surgery using veins, and more. It intends to provide data on cell signaling to help improve therapies for chronic venous insufficiency and other vascular diseases, such as deep vein thrombosis. The Principal Investigator will engage students through seminars, workshops, and online resources. The project will also support education, outreach, workforce development, and entrepreneurship initiatives, including activities for K–12 students and those at Primarily Undergraduate Institutions. In this BRITE Relaunch project, objective 1 looks to generate and share the first mechanobiological characterization of venous valve leaflet endothelial and interstitial cells, including baseline in-situ and in-vitro data and responses to physiologic and pathologic biophysical stimuli (e.g., cyclic stretch, fluid shear stress). Datasets will cover morphological analysis, growth kinetics, immunofluorescent staining (focused on mechanotransduction proteins), PCR-based mRNA quantification, Western blot protein levels, and atomic force microscopy measurements of cell stiffness. Objective 2 seeks to provide the first data on early mechanobiological effects of hypertension on ex-vivo cultured venous valves. These datasets look to build on Objective 1 by adding biaxial mechanical testing and confocal scans to map protein expression changes to stresses and strains under normal and elevated pressures and flows. Objective 3 intends to develop and openly share multiscale FSI models to explore venous valve degeneration. These new tools and insights intend to create the first cellular-level basis for understanding venous valve degeneration and its role in chronic venous insufficiency, benefiting both science and society. Together, these efforts intend to significantly advance the biomechanics and mechanobiology of venous valves and set the stage for future breakthroughs in venous disease prevention and treatment. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.