Meox1 accelerates myocardial hypertrophic decompensation through Gata4

Area of Science:

• Cardiology
• Molecular Biology
• Genetics

Background:

• Pathological hypertrophy leads to heart failure through gene network dysregulation and reactivation of foetal gene programs.
• Mesenchyme homeobox 1 (Meox1) is a foetal gene program component, but its role in pathological hypertrophy is unclear.

Purpose of the Study:

• To investigate the effect of Meox1 on familial and pressure overload-induced pathological hypertrophy.
• To elucidate the mechanism by which Meox1 influences cardiac hypertrophy.

Main Methods:

• Gene expression analysis (DGE, real-time PCR) in mouse models and human samples.
• Echocardiography, histopathology, and molecular marker assessment.
• Bioinformatics, promoter activity assays, and chromatin immunoprecipitation (ChIP) to identify and validate Meox1 targets.

Main Results:

• Meox1 expression is upregulated in various models of cardiac hypertrophy and in human hypertrophic cardiomyopathy (HCM) patients.
• Meox1 overexpression worsened cardiac hypertrophy phenotypes, while Meox1 knockdown ameliorated them.
• Gata4 was identified as a direct downstream transcriptional target of Meox1.

Conclusions:

• Meox1 exacerbates pathological hypertrophy and heart failure by activating Gata4.
• Meox1 and other foetal genes form a network that presents therapeutic targets for pathological hypertrophy.