Document Detail


Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy.
MedLine Citation:
PMID:  17438289     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
Related Documents :
2485029 - Physiologic versus pathologic hypertrophy and the pressure-overloaded myocardium.
15913489 - Is hypertension a prothrombotic state?
6450029 - Left ventricular function in chronic obstructive pulmonary disease.
8166049 - Molecular basis of regression of cardiac hypertrophy.
8829959 - Biological adaptation of the myocardium to chronic mechanical overload. molecular deter...
12106939 - Myocardial contraction fraction: a volumetric index of myocardial shortening by freehan...
17462389 - Video-assisted bilateral epicardial pulmonary vein isolation for the treatment of lone ...
17653519 - Increased prevalence of ventricular fibrillation in patients with type 2 diabetes melli...
12676879 - Ectonucleotidase in sympathetic nerve endings modulates atp and norepinephrine exocytos...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-04-16
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  104     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-04-25     Completed Date:  2007-06-06     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7074-9     Citation Subset:  IM    
Affiliation:
Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, 2103 Cornell Road, Room 4-503, Cleveland, OH 44106, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure
Cell Size
DNA-Binding Proteins / genetics*,  metabolism*
GATA4 Transcription Factor / metabolism
Gene Expression Profiling
Gene Expression Regulation
Gene Targeting
Humans
Hypertrophy
Kruppel-Like Transcription Factors / genetics*,  metabolism*
Mice
Myocytes, Cardiac / pathology*
Nuclear Proteins / genetics,  metabolism
RNA, Messenger / genetics,  metabolism
Rats
Recombination, Genetic / genetics
Transcription Factors / genetics,  metabolism
Transcription, Genetic
Grant Support
ID/Acronym/Agency:
DK 064950/DK/NIDDK NIH HHS; F32 HL 077052/HL/NHLBI NIH HHS; F32 HL 78183/HL/NHLBI NIH HHS; HL 72952/HL/NHLBI NIH HHS; HL 75427/HL/NHLBI NIH HHS; HL 76754/HL/NHLBI NIH HHS; P01 HL 48743/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/GATA4 Transcription Factor; 0/KLF15 protein, human; 0/Klf15 protein, mouse; 0/Klf15 protein, rat; 0/Kruppel-Like Transcription Factors; 0/Nuclear Proteins; 0/RNA, Messenger; 0/Transcription Factors
Comments/Corrections
Erratum In:
Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13851
Note: Pinto, Yigal [corrected to Pinto, Yigal M]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Recruitment of an inhibitory hippocampal network after bursting in a single granule cell.
Next Document:  Vitellogenin, juvenile hormone, insulin signaling, and queen honey bee longevity.