Why muscle cells in the aorta may cause narrowing above the aortic valve
Official title: Investigating altered smooth muscle cell mechanotransduction as a cause of supravalvular aortic stenosis
Funded at Washington University · NIH-11238014 · Data updated 2026-11-12
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 start | December 1, 2022 |
| Project end | November 30, 2026 |
| Funding year | 2026 |
| Award (this year) | $388,750 |
| NIH project number | 5R01HL166448-04 |
| Project ID | NIH-11238014 on NIH RePORTER |
Who could benefit from this research
✓Could help
People with supravalvular aortic stenosis or known ELN (elastin) mutations, including affected children and adults, would be the most directly relevant group.
✕Less likely to help
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.
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.
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 gone: 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
-
Washington University
Saint Louis, United States Active
Researchers
- Principal investigator: Wagenseil, Jessica — Washington University
- Study coordinator: Wagenseil, Jessica
Related research
Other NIH-funded projects on the same topics.
-
Investigating how stiffening of the aorta from elastin loss causes SVAS
A new NIH grant is exploring why elastin loss leads to supravalvular aortic stenosis and how abnormal smooth muscle cell signaling causes the aorta to narrow in children.
-
Risk prediction for aortic stenosis and how statins might help in adults 75 and older
This grant seeks to identify which adults over 75 are at high risk for aortic valve disease and how statin therapy could influence that risk.
-
AI-powered screening and monitoring for aortic stenosis in older adults
A powerful new AI-based approach uses a simple heart rhythm test and a hand-held ultrasound to detect and monitor advanced aortic valve narrowing in people aged 65 and older.
-
Linking normal aortic valve blood flow patterns to risk of aortic valve narrowing
This grant studies how normal differences in how the aortic valve moves and carries blood might influence who develops aortic stenosis.
-
Chronic Kidney Disease and Aortic Valve Disease: Understanding How Kidney Disease Influences Aortic Stenosis
This grant looks at how chronic kidney disease may affect the progression of aortic stenosis and whether we can find ways to slow it down for adults with kidney issues.
-
Advanced non-invasive imaging to understand aortic stenosis biology
Aging adults with aortic stenosis may benefit from new imaging-based research to slow disease progression and reduce need for valve procedures.
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.