title: Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy.
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.
authors: Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine, 2103 Cornell Road, Room 4-503, Cleveland, OH 44106, USA.
authors: Sudeshna
authors: S
authors: Fisch
authors: Susan
authors: S
authors: Gray
authors: Stephane
authors: S
authors: Heymans
authors: Saptarsi M
authors: SM
authors: Haldar
authors: Baiqiu
authors: B
authors: Wang
authors: Otmar
authors: O
authors: Pfister
authors: Lei
authors: L
authors: Cui
authors: Ajay
authors: A
authors: Kumar
authors: Zhiyong
authors: Z
authors: Lin
authors: Sucharita
authors: S
authors: Sen-Banerjee
authors: Hiranmoy
authors: H
authors: Das
authors: Christine A
authors: CA
authors: Petersen
authors: Ulrike
authors: U
authors: Mende
authors: Barbara A
authors: BA
authors: Burleigh
authors: Yan
authors: Y
authors: Zhu
authors: Yigal M
authors: YM
authors: Pinto
authors: Yigal
authors: Y
authors: Pinto
authors: Ronglih
authors: R
authors: Liao
authors: Mukesh K
authors: MK
authors: Jain
mesh_terms: D000818:Animals; D001794:Blood Pressure; D048429:Cell Size; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D050991:GATA4 Transcription Factor / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018390:Gene Targeting; D006801:Humans; D006984:Hypertrophy; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D032383:Myocytes, Cardiac / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011995:Recombination, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; C414172:KLF15 protein, human; C467418:Klf15 protein, mouse; C520013:Klf15 protein, rat; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors