# Regulation of Cardiac Signaling by Class I Histone Deacetylases

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $385,773

## Abstract

Project Summary/Abstract
It is estimated that half of the ~5 million patients in the United States who suffer from heart failure (HF) have
HF with preserved ejection fraction (HFpEF), which is also referred to as diastolic heart failure. Hypertension
is a major risk factor for the development of HFpEF. Unfortunately, large clinical trials have revealed that
standard-of-care HF medications fail to reduce hospitalization rates or improve lifespan in patients with HFpEF.
Thus, HFpEF remains a major unmet medical need. Our group has a longstanding interest in elucidating the
cardiac functions of a family of enzymes known as histone deacetylases (HDACs), which serve crucial roles as
epigenetic regulators of gene expression. Our preliminary data demonstrate remarkable ability of a small
molecule HDAC inhibitor to prevent and reverse diastolic cardiac dysfunction in rodent models of systemic
hypertension. Surprisingly, HDAC inhibition appears to improve diastolic function of the heart by enhancing
relaxation of the contractile units (myofibrils), revealing a non-canonical, non-epigenetic function for HDACs in
the control of cardiac relaxation. Three independent specific aims are designed to significantly extend this new
field of cardiac research, and test the overall hypothesis that non-genomic actions of HDACs govern
relaxation of the heart, and are critically involved in the pathogenesis of HFpEF.

## Key facts

- **NIH application ID:** 10219331
- **Project number:** 5R01HL116848-08
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Timothy McKinsey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $385,773
- **Award type:** 5
- **Project period:** 2013-08-08 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219331

## Citation

> US National Institutes of Health, RePORTER application 10219331, Regulation of Cardiac Signaling by Class I Histone Deacetylases (5R01HL116848-08). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10219331. Licensed CC0.

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