Why muscle cells in the aorta may cause narrowing above the aortic valve
Investigating altered smooth muscle cell mechanotransduction as a cause of supravalvular aortic stenosis
Researchers are looking at whether changes in how aortic wall muscle cells sense stretch lead to supravalvular aortic stenosis in people with elastin (ELN) gene mutations.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Washington University NIH-funded |
| Lab location | 1 site (Saint Louis, United States) |
| Project ID | NIH-11238014 on NIH RePORTER |
What this research studies
From a patient's point of view, this work uses a mouse model that mimics elastin loss and lab studies of aortic smooth muscle cells to see how reduced elastin changes artery stiffness and cell stretch. The team measures mechanosensitive Piezo channel activity, calcium signaling, and downstream YAP/TAZ and CTGF pathways that control cell growth and movement. They compare gene and protein changes and cell behaviors to link altered mechanics with the focal narrowing seen in SVAS. The goal is to understand the chain of events that could point to ways to prevent or slow aortic narrowing.
Who could benefit from this research
Good fit: People with supravalvular aortic stenosis or known ELN (elastin) mutations, including affected children and adults, would be the most directly relevant group.
Not a fit: Patients with aortic narrowing from other causes (for example age-related calcific aortic valve disease) or without ELN mutations may not see direct benefit from this work.
Why it matters
Potential benefit: Could identify molecular pathways or targets that lead to new treatments to prevent or slow aortic narrowing in people with ELN-related SVAS.
How similar studies have performed: Prior studies have linked mechanosensitive channels and YAP/TAZ signaling to vascular cell behavior, but applying Piezo-mediated mechanotransduction specifically to ELN-related SVAS is relatively novel.
Where this research is happening
Saint Louis, United States
- Washington University — Saint Louis, United States (Active)
Researchers
- Principal investigator: Wagenseil, Jessica — Washington University
- Study coordinator: Wagenseil, Jessica
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.