# Role of cardiomyocyte KLF5 in heart failure.

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2021 · $471,576

## Abstract

ABSTRACT
 Myocardial ischemia (MI) leads to cardiac remodeling and heart failure (HF). Multiple mechanisms and
cellular pathways affect pathophysiology of the disease and therefore challenge identification of effective
treatments. Our preliminary findings in human myocardial samples of advanced HF and mouse ischemic
hearts and cardiomyocytes suggest transcriptional factor Krüppel-like factor 5 (KLF5) as a central component
of ischemic HF. Specifically, we propose that KLF5 regulates ceramide biosynthesis and miR30 expression,
both of which have been associated with worse prognosis in HF. Based on our previous study, which showed
that KLF5 regulates cardiac metabolism and other studies showing that cardiac metabolism is altered in
various types of cardiomyopathy, we assessed whether altered KLF5 expression may be involved in adverse
cardiac remodeling. We showed in human myocardial samples and various mouse models that MI increased
KLF5 expression, which eventually stimulates serine palmitoyl-transferase and biosynthesis of ceramides, as
well as it suppresses expression of all miR30s. On the other hand, suppression of KLF5 was protective.Based
on these findings, we hypothesize that KLF5 inhibition will alleviate ischemic HF via suppression of
ceramide synthesis and upregulation of miR30 expression. To address our hypothesis, we have designed
the following Specific Aims:
 Aim 1: Investigate the mechanism via which KLF5 regulates cardiac ceramide metabolism and
causes cardiac dysfunction.
 Aim 2: Elucidate the involvement of miR30 suppression in mediating the cardiotoxic effect of
KLF5 in MI.
 Aim 3: Explore the therapeutic potential of KLF5 inhibition in HF
 The proposed study will identify for the first time KLF5 as a central component of cardiac pathophysiology
in MI and will indicate KLF5 suppression as a potential therapeutic target for ischemic HF.

## Key facts

- **NIH application ID:** 10136715
- **Project number:** 5R01HL151924-02
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Konstantinos Drosatos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $471,576
- **Award type:** 5
- **Project period:** 2020-04-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136715

## Citation

> US National Institutes of Health, RePORTER application 10136715, Role of cardiomyocyte KLF5 in heart failure. (5R01HL151924-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10136715. Licensed CC0.

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