# Role of Adiponectin in Reversal of Age-related Vascular Dysfunction

> **NIH NIH R01** · KANSAS STATE UNIVERSITY · 2024 · $322,722

## Abstract

Aging is a primary risk factor for development of cardiovascular dysfunction and disease. The hallmarks
of vascular aging are endothelial dysfunction, development of a synthetic, atherosclerotic phenotype in
smooth muscle, and arterial inflammation and stiffening. We have shown that aerobic exercise training
can mitigate or reverse age-related vascular dysfunction and adverse arterial remodeling; however, the
cellular signals that contribute to the ability of exercise training to promote macro- and microvascular
resiliency remain unidentified. Similarly, the mechanisms whereby exercise training reverses age-
related vascular dysfunction remain unknown. Reduced circulating adiponectin has been associated with
the adverse vascular changes that occur with advancing age; however, a role for adiponectin in age-
related vascular dysfunction has not been demonstrated. We have reported that circulating adiponectin
levels increase in response to late-life exercise training; however, a direct role for adiponectin signaling
in reversal of age-related vascular dysfunction by exercise training has not been demonstrated. We
propose to test a central hypothesis that 1) loss of adiponectin is a critical contributor to age-
related vascular dysfunction and adverse arterial remodeling, and 2) adiponectin contributes to
the ability of exercise training to promote vascular resiliency and reverse age-related vascular
dysfunction and age-related adverse vascular remodeling. We propose to study sedentary and
exercise trained mice, across the murine lifespan, to determine 1) the impact of loss- and gain-of-function
of adiponectin on ceramide/sphingosine signaling in the endothelium of the microvasculature of the heart
and skeletal muscle, 2) the impact of loss- and gain-of-function of adiponectin on development of a
senescence-associated synthetic phenotype in vascular smooth muscle and contractile dysfunction the
microvasculature of the heart and skeletal muscle, and 3) the impact of loss- and gain-of-function of
adiponectin on remodeling of large arteries. Results from the proposed work will increase our
understanding of the role of adiponectin in age-related vascular dysfunction and exercise training-induced
reversal of age-related vascular dysfunction. A top biomedical research priority is to identify strategies
which promote vascular resiliency with advancing age or which reverse age-related vascular dysfunction.
The proposed work could identify 1) components of the adiponectin signaling pathway that could be
targeted for prevention of age-related vascular dysfunction, and 2) novel exercise mimetics that could be
employed for 1) promotion of vascular resiliency across the lifespan, and/or 2) reversal of age-related
vascular dysfunction.

## Key facts

- **NIH application ID:** 11160280
- **Project number:** 7R01HL166591-03
- **Recipient organization:** KANSAS STATE UNIVERSITY
- **Principal Investigator:** JUDY M DELP
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $322,722
- **Award type:** 7
- **Project period:** 2023-02-15 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11160280

## Citation

> US National Institutes of Health, RePORTER application 11160280, Role of Adiponectin in Reversal of Age-related Vascular Dysfunction (7R01HL166591-03). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/11160280. Licensed CC0.

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