Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy

Sudeshna Fisch; Susan Gray; Stephane Heymans; Saptarsi M Haldar; Baiqiu Wang; Otmar Pfister; Lei Cui; Ajay Kumar; Zhiyong Lin; Sucharita Sen-Banerjee; Hiranmoy Das; Christine A Petersen; Ulrike Mende; Barbara A Burleigh; Yan Zhu; Yigal M Pinto; Yigal Pinto; Ronglih Liao; Mukesh K Jain

doi:10.1073/pnas.0701981104

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Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy

Journal article

Open access

Peer reviewed

Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy

Sudeshna Fisch, Susan Gray, Stephane Heymans, Saptarsi M Haldar, Baiqiu Wang, Otmar Pfister, Lei Cui, Ajay Kumar, Zhiyong Lin, Sucharita Sen-Banerjee, …

Proceedings of the National Academy of Sciences - PNAS, Vol.104(17), pp.7074-7079

04/24/2007

DOI: 10.1073/pnas.0701981104

PMCID: PMC1855421

PMID: 17438289

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Abstract

Cardiac hypertrophy is a common response to injury and hemodynamic stress and an important harbinger of heart failure and death. Herein, we identify the Kruppel-like factor 15 (KLF15) as an inhibitor of cardiac hypertrophy. Myocardial expression of KLF15 is reduced in rodent models of hypertrophy and in biopsy samples from patients with pressure-overload induced by chronic valvular aortic stenosis. Overexpression of KLF15 in neonatal rat ventricular cardiomyocytes inhibits cell size, protein synthesis and hypertrophic gene expression. KLF15-null mice are viable but, in response to pressure overload, develop an eccentric form of cardiac hypertrophy characterized by increased heart weight, exaggerated expression of hypertrophic genes, left ventricular cavity dilatation with increased myocyte size, and reduced left ventricular systolic function. Mechanistically, a combination of promoter analyses and gel-shift studies suggest that KLF15 can inhibit GATA4 and myocyte enhancer factor 2 function. These studies identify KLF15 as part of a heretofore unrecognized pathway regulating the cardiac response to hemodynamic stress.

Gene Targeting

Blood Pressure

GATA4 Transcription Factor - metabolism

Humans

RNA, Messenger - genetics

Gene Expression Regulation

Rats

Cell Size

Nuclear Proteins - metabolism

Gene Expression Profiling

Transcription Factors - genetics

DNA-Binding Proteins - genetics

RNA, Messenger - metabolism

DNA-Binding Proteins - metabolism

Transcription Factors - metabolism

Myocytes, Cardiac - pathology

Animals

Kruppel-Like Transcription Factors - metabolism

Recombination, Genetic - genetics

Transcription, Genetic

Mice

Nuclear Proteins - genetics

Kruppel-Like Transcription Factors - genetics

Hypertrophy

Details

Title: Subtitle: Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy
Creators: Sudeshna Fisch - Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, 2103 Cornell Road, Room 4-503, Cleveland, OH 44106, USA
Susan Gray
Stephane Heymans
Saptarsi M Haldar
Baiqiu Wang
Otmar Pfister
Lei Cui
Ajay Kumar
Zhiyong Lin
Sucharita Sen-Banerjee
Hiranmoy Das
Christine A Petersen
Ulrike Mende
Barbara A Burleigh
Yan Zhu - St. Elizabeth's Medical Center
Yigal M Pinto
Yigal Pinto
Ronglih Liao
Mukesh K Jain
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.104(17), pp.7074-7079
DOI: 10.1073/pnas.0701981104
PMID: 17438289
PMCID: PMC1855421
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences; United States
Grant note: F32 HL077052 / NHLBI NIH HHS R01 HL075427 / NHLBI NIH HHS K01 DK064950 / NIDDK NIH HHS R01 HL072952 / NHLBI NIH HHS R01 HL076754 / NHLBI NIH HHS HL 72952 / NHLBI NIH HHS F32 HL078183 / NHLBI NIH HHS HL 76754 / NHLBI NIH HHS F32 HL 78183 / NHLBI NIH HHS P01 HL048743 / NHLBI NIH HHS HL 75427 / NHLBI NIH HHS DK 064950 / NIDDK NIH HHS F32 HL 077052 / NHLBI NIH HHS P01 HL 48743 / NHLBI NIH HHS
Language: English
Date published: 04/24/2007
Academic Unit: Epidemiology; Internal Medicine
Record Identifier: 9983995019602771

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