TY - JOUR
T1 - Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy
AU - Fisch, Sudeshna
AU - Gray, Susan
AU - Heymans, Stephane
AU - Haldar, Saptarsi M.
AU - Wang, Baiqiu
AU - Pfister, Otmar
AU - Cui, Lei
AU - Kumar, Ajay
AU - Lin, Zhiyong
AU - Sen-Banerjee, Sucharita
AU - Das, Hiranmoy
AU - Petersen, Christine A.
AU - Mende, Ulrike
AU - Burleigh, Barbara A.
AU - Zhu, Yan
AU - Pinto, Yigal M.
AU - Liao, Ronglih
AU - Jain, Mukesh K.
PY - 2007
Y1 - 2007
N2 - 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
AB - 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
U2 - https://doi.org/10.1073/pnas.0701981104
DO - https://doi.org/10.1073/pnas.0701981104
M3 - Article
C2 - 17438289
SN - 0027-8424
VL - 104
SP - 7074
EP - 7079
JO - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
IS - 17
ER -