Meox1 Promotes Cardiac Fibrosis and Pathological Remodeling following Myocardial Infarction through Cthrc1/p-Smad2/3...

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Fibrosis Research

Background:

• Myocardial infarction (MI) causes cardiac fibrosis, ventricular remodeling, and heart failure.
• Mesenchyme homeobox 1 (Meox1) is a known fibroblast activator, but its role in MI-induced fibrosis is unclear.

Purpose of the Study:

• To investigate the role of Meox1 in cardiac fibrosis and remodeling following MI.
• To elucidate the underlying molecular mechanisms of Meox1 in this process.

Main Methods:

• Meox1 expression was analyzed in mouse models of MI and in primary cardiac fibroblasts (CFs) stimulated with TGF-β1.
• Meox1 was knocked down or overexpressed in CFs and in vivo models.
• Collagen triple helix repeat containing 1 (Cthrc1) and Smad2/3 phosphorylation were assessed.

Main Results:

• Meox1 expression increased in activated fibroblasts (myofibroblasts, Myofbs) post-MI and with TGF-β1 stimulation.
• Meox1 knockdown attenuated cardiac fibrosis, adverse remodeling, and improved cardiac function post-MI.
• Meox1 promoted CFs activation, proliferation, migration, and fibrotic gene expression by transcriptionally activating Cthrc1, leading to Smad2/3 phosphorylation.

Conclusions:

• Meox1 plays a key role in promoting cardiac fibrosis and heart failure post-MI.
• The Meox1/Cthrc1/p-Smad2/3 pathway mediates the transformation of CFs to Myofbs.
• This pathway represents a potential therapeutic target for treating cardiac fibrosis and remodeling in MI patients.