# Therapeutic activation of AMPK for the aging right heart

> **NIH NIH K01** · UNIVERSITY OF WYOMING · 2020 · $132,102

## Abstract

ABSTRACT/PROJECT SUMMARY
The overarching goal of this application is to provide Dr. Bruns the scientific and career
development for a successful independent research career in the field of cardiac aging, with a
specific focus on the right ventricle. Heart failure (HF) is a major public health concern within
aging populations. In age-related left-sided heart failure as well as other clinical contexts, right
ventricular (RV) dysfunction is the strongest predictor of mortality. However, despite the clear
link between right heart function and survival, very little is known about RV function with age.
This knowledge gap underscores the need to assess the impact of aging on the RV with the
long-term goal of developing therapeutics that target declining RV function. Although no RV-
directed therapies exist, epidemiological data and preliminary data from our lab suggest that
activation of AMP-activated protein kinase (AMPK) may be beneficial through novel and direct
action on the cardiac contractile apparatus. Accordingly, the global hypothesis of this project is
that aging exacerbates RV dysfunction, and contractile apparatus-mediated mechanisms can be
exploited for novel therapies for the aging right heart. To address this hypothesis, we propose
two specific aims: 1) to assess the impact of age on two models of right heart failure- isolated
RV pressure overload and hypobaric hypoxia (pulmonary hypertension)-induced RV
dysfunction, a highly significant and translationally important disease in cardiovascular aging;
and 2) to determine if activation of AMPK attenuates cardiac dysfunction in aged mice, and the
mechanisms by which this occurs. We will investigate AMPK activation as a novel RV-directed
therapy in cardiac aging using both genetic and pharmaceutical approaches, facilitating the
elucidation of molecular mechanisms underlying cardiac dysfunction. The mentorship team and
career development assembled to answer this translationally important question will provide
training in aging biology, molecular genetics, and myofilament mechanics, important skills for a
career as an independent cardiac aging scientist. Together, successful completion of this
proposal will propel scientific independence by providing the training, mentorship, and scientific
guidance upon which to build a successful research agenda in the field of cardiac aging biology.

## Key facts

- **NIH application ID:** 9876894
- **Project number:** 5K01AG058810-02
- **Recipient organization:** UNIVERSITY OF WYOMING
- **Principal Investigator:** Danielle Reuland Bruns
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $132,102
- **Award type:** 5
- **Project period:** 2019-03-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9876894

## Citation

> US National Institutes of Health, RePORTER application 9876894, Therapeutic activation of AMPK for the aging right heart (5K01AG058810-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9876894. Licensed CC0.

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