Fibrotic aortic valve stenosis (FAVS) is a heart disease that causes thickening and hardening of the valve leaflets, leading to impaired function, reduced blood flow, and ultimately, heart failure. Currently, there are no non-surgical therapies and the only valve replacements are made of rigid, synthetic materials or decellularized xenografts, both of which cannot repair or grow with younger patients. With tens of thousands of replacement surgeries being completed annually in the United States, this is an area of medicine that would benefit from a better understanding of this disease at the cellular level- potentially elucidating preventative treatments and therapeutics.
Until recently, AVS was thought of as degeneration of the valve tissue with patient age. However, it is now understood to be actively mediated by the resident cells, valvular interstitial cells (VICs). VICs are generally found in a quiescent fibroblast state that can be activated to a secretory myofibroblast phenotype when the valve is injured. These myofibroblasts are critical in repairing the valve to maintain function and homeostasis. With chronic valve injury and inflammation, the regulation of the myofibroblast phenotype can be lost and lead to excess matrix deposition, hardening of the valve, and eventually, further differentiation of the VICs into osteoblasts (i.e., bone cells).
Our group is trying to understand the cellular drivers behind FAVS, including biochemical signaling pathways in addition to mechanical cues associated with healthy versus pathological phenotypic changes seen in VICs. To do so, we are using PEG based hydrogels so that the biophysical and biochemical microenvironment may be acutely controlled based on the hypothesis at hand.