# Integrins as regulators of vascular contractility in aged resistance arteries

> **NIH NIH R03** · TEXAS A&M UNIVERSITY · 2020 · $73,553

## Abstract

PROJECT SUMMARY
Slowing or preventing age-induced arterial vasomotor dysfunction that is associated with an increased risk for
cardiovascular diseases remains a significant clinical challenge. Increasing evidence supports that changes in
the extracellular matrix alone are insufficient to fully account for vascular stiffness and loss of arterial contractility
in aging, and a new concept has emerged that vascular smooth muscle (VSM) cells are important contributors
to age-induced arterial dysfunction. The role of integrin-mediated signaling to the regulation of cytoskeletal
contractility in the aged VSM cells remains largely unknown. Therefore, there is a critical need to determine the
mechanisms whereby age-induced alterations of integrin signaling contributes to decreased vascular contractility
in aged resistance arteries. Our long-term goal is to identify mechanisms responsible for the age-induced decline
in arterial contractility. The overall objective for this proposal is to determine the mechanistic contribution of
integrin signaling to impaired VSM contractility in aged resistance arteries. Our central hypothesis is that age-
induced alteration of integrin function impairs recruitment of key adhesion proteins and stress fiber formation
resulting in reduced VSM contractility in resistance arteries. We have formulated this hypothesis on the basis of
our strong preliminary data indicating that aging decreases key contractile and adhesion proteins. These age-
induced changes contribute to the conversion of VSM cells to a synthetic phenotype, which is characterized by
reduced VSM cell contractility and mechanosensing in resistance arteries. The rationale for the proposed
research is that a mechanistic understanding of how aging affects integrin function and VSM contractility will
enable the identification of novel targets to prevent or reverse age-associated loss of vascular contractility. The
hypothesis will be tested by pursuing the following two specific aims: (1) Determine the contribution of integrins
to the regulation of cell-matrix adhesion in aged VSM; (2) Determine the contribution of integrin signaling to
stress fiber formation in aged VSM. The approach will involve the use of real-time, high-resolution fluorescence
and atomic force microscopy in live cells, and ex-vivo functional experiments in resistance arteries from young
and old, male and female, Fischer 344 rats. The proposed research is innovative because it represents a novel
mechanism in aging by which integrin adhesion regulates ROCK/MRTF-A/SRF activation by controlling actin
stress fiber formation and actomyosin activation. The proposed research is significant because understanding
the mechanism by which integrin function regulates VSM contractility in aged resistance arteries will fill a gap in
knowledge regarding age progression. Ultimately, this work will be critical for future studies underlying age-
induced loss of contractile function by giving a new direction for thera...

## Key facts

- **NIH application ID:** 9975078
- **Project number:** 5R03AG064551-02
- **Recipient organization:** TEXAS A&M UNIVERSITY
- **Principal Investigator:** Andreea Trache
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $73,553
- **Award type:** 5
- **Project period:** 2019-07-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975078

## Citation

> US National Institutes of Health, RePORTER application 9975078, Integrins as regulators of vascular contractility in aged resistance arteries (5R03AG064551-02). Retrieved via AI Analytics 2026-06-15 from https://api.ai-analytics.org/grant/nih/9975078. Licensed CC0.

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