@article{e089806c9c614cc38ee11b5a7a875899,
title = "Cardiac Myocyte KLF5 Regulates Ppara Expression and Cardiac Function",
abstract = "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 Kr{\"u}ppel-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.",
keywords = "PPAR alpha, cardiac myocyte, fatty acids, heart, heart failure",
author = "Konstantinos Drosatos and Pollak, {Nina M.} and Pol, {Christine J.} and Panagiotis Ntziachristos and Florian Willecke and Valenti, {Mesele Christina} and Trent, {Chad M.} and Yunying Hu and Shaodong Guo and Iannis Aifantis and Goldberg, {Ira J.}",
note = "Funding Information: This study was supported by National Heart, Lung, and Blood Institute Pathway to Independence R00 award HL112853 (K. Drosatos), HL45095 and HL73029 (I.J. Goldberg), the Fonds zur F{\"o}rderung der wissenschaftlichen Forschung (FWF) project DK-MCD W1226 of the Austrian Science Fund (FWF; N.M. Pollak), fellowships from Lady Tata Memorial Trust for leukemia, the American Society of Hematology, a Pathway to Independence award by the National Institutes of Health K99CA188293 (P. Ntziachristos), a research fellowship by the Deutsche Forschungsgemeinschaft (F. Willecke), the William Lawrence and Blanche Hughes Foundation, the Leukemia & Lymphoma Society, the Ralph S. French Charitable Foundation Trust, the Chemotherapy Foundation, the V Foundation for Cancer Research, and the St. Baldrick''s Foundation (I. Aifantis). I. Aifantis is a Howard Hughes Medical Institute''s Early Career Scientist. Funding Information: This study was supported by National Heart, Lung, and Blood Institute Pathway to Independence R00 award HL112853 (K. Drosatos), HL45095 and HL73029 (I.J. Goldberg), the Fonds zur F?rderung der wissenschaftlichen Forschung (FWF) project DK-MCD W1226 of the Austrian Science Fund (FWF; N.M. Pollak), fellowships from Lady Tata Memorial Trust for leukemia, the American Society of Hematology, a Pathway to Independence award by the National Institutes of Health K99CA188293 (P. Ntziachristos), a research fellowship by the Deutsche Forschungsgemeinschaft (F. Willecke), the William Lawrence and Blanche Hughes Foundation, the Leukemia & Lymphoma Society, the Ralph S. French Charitable Foundation Trust, the Chemotherapy Foundation, the V Foundation for Cancer Research, and the St. Baldrick''s Foundation (I. Aifantis). I. Aifantis is a Howard Hughes Medical Institute''s Early Career Scientist. Publisher Copyright: {\textcopyright} 2015 American Heart Association, Inc.",
year = "2016",
month = jan,
day = "22",
doi = "10.1161/CIRCRESAHA.115.306383",
language = "English (US)",
volume = "118",
pages = "241--253",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "2",
}
