Cardiac Myocyte KLF5 Regulates Ppara Expression and Cardiac Function

K Drosatos; Nina M Pollak; C J Pol; P Ntziachristos; F Willecke; M C Valenti; C M Trent; Y Hu; S Guo; I Aifantis; I J Goldberg

doi:10.1161/CIRCRESAHA.115.306383

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Cardiac Myocyte KLF5 Regulates Ppara Expression and Cardiac Function

Journal article

Peer reviewed

Cardiac Myocyte KLF5 Regulates Ppara Expression and Cardiac Function

K Drosatos, Nina M Pollak, C J Pol, P Ntziachristos, F Willecke, M C Valenti, C M Trent, Y Hu, S Guo, I Aifantis, …

Circulation Research, Vol.118(2), pp.241-253

2016

DOI: https://doi.org/10.1161/CIRCRESAHA.115.306383

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Abstract

cardiac myocyte

fatty acids

heart

heart failure

PPAR alpha

Rationale: Fatty acid oxidation is transcriptionally regulated by peroxisome proliferator-activated receptor (PPAR)α and under normal conditions accounts for 70% of cardiac ATP content. Reduced Ppara expression during sepsis and heart failure leads to reduced fatty acid oxidation and myocardial energy deficiency. Many of the transcriptional regulators of Ppara are unknown. Objective: To determine the role of Krüppel-like factor 5 (KLF5) in transcriptional regulation of Ppara. Methods and Results: We discovered that KLF5 activates Ppara gene expression via direct promoter binding. This is blocked in hearts of septic mice by c-Jun, which binds an overlapping site on the Ppara promoter and reduces transcription. We generated cardiac myocyte-specific Klf5 knockout mice that showed reduced expression of cardiac Ppara and its downstream fatty acid metabolism-related targets. These changes were associated with reduced cardiac fatty acid oxidation, ATP levels, increased triglyceride accumulation, and cardiac dysfunction. Diabetic mice showed parallel changes in cardiac Klf5 and Ppara expression levels. Conclusions: Cardiac myocyte KLF5 is a transcriptional regulator of Ppara and cardiac energetics. © 2015 American Heart Association, Inc.

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Title: Cardiac Myocyte KLF5 Regulates Ppara Expression and Cardiac Function
Authors: K Drosatos (Author) - Temple University School of Medicine, United States
Nina M Pollak (Author) - University of Graz, Austria
C J Pol (Author) - Temple University School of Medicine, United States
P Ntziachristos (Author) - New York University School of Medicine, United States
F Willecke (Author) - New York University-Langone School of Medicine, United States
M C Valenti (Author) - Temple University School of Medicine, United States
C M Trent (Author) - New York University-Langone School of Medicine, United States
Y Hu (Author) - New York University-Langone School of Medicine, United States
S Guo (Author) - Texas A & M Health Science Center, United States
I Aifantis (Author) - New York University School of Medicine, United States
I J Goldberg (Author) - New York University-Langone School of Medicine, United States
Publication details: Circulation Research, Vol.118(2), pp.241-253
Publisher: Lippincott Williams & Wilkins
Date published: 2016
DOI: 10.1161/CIRCRESAHA.115.306383
ISSN: 0009-7330
Organisation Unit: School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99450415102621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease

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