How epigenetic changes and Notch signaling cause aorta narrowing from elastin loss
Epigenetic-mediated Notch pathway activation promotes elastin aortopathy
['FUNDING_R01'] · YALE UNIVERSITY · NIH-11257998
Looks into whether blocking a specific Notch signal can reduce artery wall thickening in people with elastin-related aorta narrowing such as supravalvular aortic stenosis and Williams-Beuren syndrome.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | YALE UNIVERSITY (nih funded) |
| Locations | 1 site (NEW HAVEN, UNITED STATES) |
| Trial ID | NIH-11257998 on ClinicalTrials.gov |
What this research studies
From a patient's point of view, researchers are using mouse models that carry elastin (ELN) defects to see how changes to gene regulation (epigenetics) turn on the Notch pathway and cause artery muscle cells to overgrow and narrow the aorta. The team will block NOTCH3 signaling in these models and examine artery structure, cell proliferation, and molecular markers to see if hypermuscularization is reduced. They will map the epigenetic changes that increase JAG1-NOTCH3 activity and test whether modulating those signals prevents or reverses aortopathy. The goal is to find targets that could lead to medicines that reduce the need for high-risk surgery for SVAS and related elastin aortopathies.
Who could benefit from this research
Good fit: People with supravalvular aortic stenosis or Williams-Beuren syndrome caused by ELN (elastin) mutations are the most relevant group for these findings.
Not a fit: Patients whose aortic disease is due to other causes (for example atherosclerotic disease) or those needing immediate surgical repair are unlikely to benefit directly from this basic mechanistic work.
Why it matters
Potential benefit: Could identify drug targets to prevent or lessen aortic narrowing in people with elastin defects, potentially reducing the need for risky surgery.
How similar studies have performed: Earlier animal work from this team showed that inhibiting NOTCH3 reduced aortic smooth muscle overgrowth in elastin-deficient mice, but this approach has not yet been developed into human treatments.
Where this research is happening
NEW HAVEN, UNITED STATES
- YALE UNIVERSITY — NEW HAVEN, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: GREIF, DANIEL — YALE UNIVERSITY
- Study coordinator: GREIF, DANIEL
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.
Conditions: Arterial Obstructive Diseases, Arterial Obstructive Disorder, Arterial Occlusive Diseases, Arterial Occlusive Disorder, Beuren syndrome