# Cadherin-11 in calcific aortic valve disease

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2024 · $56,991

## Abstract

PROJECT SUMMARY/ABSTRACT
Age-related heart valve disease is the 3rd leading cause of cardiovascular disease and is especially prevalent
among the elderly. Studies have shown that degenerative aortic valve disease affects over 25% of people over
65 years of age, and eventually leads to calcific aortic valve disease (CAVD). There is no effective medical
therapy that modifies the progression of CAVD. CAVD is believed to be primarily driven by the valve interstitial
cells (VICs). Briefly, when these normally quiescent VICs become ‘activated’ via unknown mechanisms, they
become myofibroblasts and express smooth muscle α–actin and cadherin-11 (CDH11). We have generated
robust evidence over the past decade to advance CDH11 as a prime candidate for CAVD therapy. Our
hypothesis is that CDH11 is the mechanobiological driver of the majority of cases of CAVD and that targeting it
can halt the progression and possibly reverse CAVD. Therefore, we propose three aims to advance targeting of
CDH11 for treatment of CAVD. Aim 1: Clarify the cell-cell-specific mechanism of CDH11 engagement that leads
to CAVD. Aim 2: Determine if targeting CDH11 can halt or reverse AS progression. Aim 3: Evaluate circulating
CDH11 as a biomarker to identify interventional timing in AS patients. At the conclusion of these aims, we will
have clarified the precise cell-cell interaction by which CDH11 drives CAVD, established if targeting CDH11 after
the development of CAVD can halt or reverse the pathology, and determined if circulating CDH11 can be used
as a biomarker in the progression of AS to guide a future clinical trial.

## Key facts

- **NIH application ID:** 11045158
- **Project number:** 3R01HL170546-01S1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** William D Merryman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $56,991
- **Award type:** 3
- **Project period:** 2024-02-15 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11045158

## Citation

> US National Institutes of Health, RePORTER application 11045158, Cadherin-11 in calcific aortic valve disease (3R01HL170546-01S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11045158. Licensed CC0.

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