Aortic Valve Disease

Nearly four million Americans over the age of 65 are living with calcific aortic valve disease (CAVD). CAVD pathogenesis is an active biological process that is untreatable by cholesterol metabolism modifying agents. Currently there are no successful biological targets or therapeutic agents that specifically target CAVD. Aortic valve cusp homeostasis and pathogenesis are regulated by complex and poorly understood interactions between resident surface valve endothelial cells (VEC) and underlying valve interstitial cell (VIC). 

Jonathan T. Butcher, Biomedical Engineering, is working to clarify the mechanisms and downstream pathophysiological relevance of these cell interactions. Butcher’s group combines novel in vitro three-dimensional co-culture models, innovative hemodynamic bioreactors, and valve cell specific conditional mouse genetics to test how two specific genes, NFκB and Notch, control homeostasis and calcific degeneration.

The completion of the project will generate significant information regarding intercellular regulation of aortic valve homeostasis and the CAVD pathogenic process. By revealing the unique phenotypic signatures of VEC and VIC, Butcher’s lab will improve precision in biological diagnostic or therapeutic strategies for valve disease.

NIH Award Number: 1R01HL143247-01

Cornell Researchers

Funding Received

$2.5 Million spanning 5 years