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 Krüppel-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

SUBMITTER: Drosatos K 

PROVIDER: S-EPMC4886555 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature