# Transcriptional regulation of cardiac pathological remodeling by REV-ERBα

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $474,695

## Abstract

Project Summary
 Heart failure (HF) is associated with a 5-year mortality of 50% and the incidence is still rising. Identifying
novel strategies to HF is of urgent clinical need. One missed opportunity is that HF is associated with a
stereotypical gene expression program, however, the current therapy focuses on improving hemodynamics and
neurohormonal milieu, the already committed gene program is not reversed. We have identified a circadian
repressor REV-ERBα, which binds near pathological driver transcription factor MEF2s in the heart and prevents
pathological gene program activation during HF. We demonstrated that pharmacological agonist of REV-ERBα
ameliorates cardiac hypertrophy and HF during a variety of stresses both as prevention and as late disease
stabilization. Cardiac deletion of REV-ERBα and b leads to exaggerated heart failure after pressure overload
and spontaneously with aging. Further, we found REV-ERBα agonist has a similar effect in human induced
pluripotent stem cells derived cardiomyocytes. We thus hypothesize that REV-ERBα inhibits cardiac pathological
remodeling through transcriptional repression at the aberrantly activated MEF2 enhancers. Our long-term goal
is to understand how REV-ERBα inhibits gene program in the cardiomyocytes and develop REV-ERBα
enhancement as a novel therapeutic strategy for HF. In this proposal, we have two specific aims towards this
goal: (1) define the role of REV-ERB in the cardiomyocytes at rest and under cardiac stress; (2) determine the
molecular basis of REV-ERBα and MEF2c interaction during cardiac remodeling. Completion of this proposal
will have significant impact in understanding gene regulation in the heart during pathological remodeling and
potentially expand our therapeutic strategies for HF treatment.

## Key facts

- **NIH application ID:** 10171416
- **Project number:** 5R01HL143067-03
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Lilei Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $474,695
- **Award type:** 5
- **Project period:** 2019-05-08 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10171416

## Citation

> US National Institutes of Health, RePORTER application 10171416, Transcriptional regulation of cardiac pathological remodeling by REV-ERBα (5R01HL143067-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10171416. Licensed CC0.

---

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