# Regulation of Mechanical Coupling in Aging Myocardium

> **NIH NIH R21** · RHODE ISLAND HOSPITAL · 2024 · $205,000

## Abstract

Project Summary
Age modifies heart structure and function, even in the absence of overt cardiovascular
disease. With age-related cardiac remodeling, the heart undergoes extensive cellular
and molecular changes that result in a stiffer less compliant heart that experiences an
overall decline in function. Yet, the human heart is capable of functioning for decades
despite minimal cell turnover or regeneration, suggesting that some mechanisms of
age-related cardiac remodeling may be compensatory and beneficial, helping sustain
heart function over our life span. Recent evidence indicates the upregulation of
cytoskeletal proteins may represent a cardioprotective mechanism in the aging heart. In
this exploratory R21 proposal, we hypothesize that enhancing the cytoskeletal
connection between N-cadherin and the cortical actin network represents an essential
compensatory mechanism to maintain force transmission in the aging mammalian heart.
To test this hypothesis, the regulation of vinculin, a force-sensitive cytoskeletal protein,
will be investigated during cardiac aging in mice. The following interrelated aims are
proposed: (1) To test the hypothesis that Abl kinase is required to maintain mechano-
electrical integrity in the aging heart. (2) To test the hypothesis that inhibition of tyrosine
phosphorylation of vinculin will perturb N-cadherin-cytoskeletal connection leading to
accelerated cardiac aging. The proposed studies will allow mechanistic insight into how
the major predisposing factor in heart disease, age, affects the remodeling of N-
cadherin junctions and mechanical coupling in the aging heart.

## Key facts

- **NIH application ID:** 10809849
- **Project number:** 1R21AG077036-01A1
- **Recipient organization:** RHODE ISLAND HOSPITAL
- **Principal Investigator:** GLENN Lawrence RADICE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $205,000
- **Award type:** 1
- **Project period:** 2024-06-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10809849

## Citation

> US National Institutes of Health, RePORTER application 10809849, Regulation of Mechanical Coupling in Aging Myocardium (1R21AG077036-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10809849. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*