BME researchers look at novel therapeutic approach to prevent hardened heart valves
Heart valve disease has few non-surgical therapeutic options. To develop strategies for treating and preventing heart valve disease, W. David Merryman, Ph.D., assistant professor of Biomedical Engineering, and colleagues are studying the cellular signaling that leads to calcification (hardening) of the aortic valve.
Previous studies have shown that the TGF-beta1 signaling pathway activates a process in aortic valve interstitial cells that is thought to cause calcification and heart valve disease. The cell surface serotonin-2B receptor also activates this process.
Now, in the November Journal of Molecular and Cellular Cardiology, the investigators report that blocking the serotonin-2B receptor (with an inhibitor drug) prevents activation of aortic valve cells and formation of calcific nodules in a cell culture system. They further show that inhibition of the serotonin-2B receptor blocks the so-called “non-canonical” TGF-beta1 signaling pathway, but not the “canonical” pathway.
The findings demonstrate that non-canonical TGF-beta1 signaling leads to pathologic activation of aortic valve cells and suggest that blocking the serotonin-2B receptor may provide a novel therapeutic approach for preventing heart valve disease.
This research was supported by grants from the American Heart Association, the National Institutes of Health (HL094707) and the National Science Foundation.
Leigh MacMillan, (615) 322-4747