REV-ERB is essential in cardiac fibroblasts homeostasis

Area of Science:

• Cardiovascular Biology
• Molecular Biology
• Fibrosis Research

Background:

• REV-ERB agonists demonstrate antifibrotic properties in various organs.
• The specific role of REV-ERB in cardiac fibroblasts is currently unknown.

Purpose of the Study:

• To investigate the function of REV-ERB alpha and beta in cardiac fibroblasts.
• To compare REV-ERB function in cardiac fibroblasts versus mouse embryonic fibroblasts.
• To assess the therapeutic potential of REV-ERB agonists in cardiac fibrosis.

Main Methods:

• Genetic deletion of REV-ERB alpha and beta in vitro.
• Analysis of cardiac fibroblast viability, proliferation, migration, and myofibroblast activation.
• Evaluation of the REV-ERB-dependent and independent effects of the agonist SR9009.

Main Results:

• REV-ERB alpha/beta double deletion in cardiac fibroblasts led to reduced viability and proliferation.
• Deletion also resulted in increased migration and myofibroblast activation.
• The REV-ERB agonist SR9009 suppressed cardiac fibroblast activation via a REV-ERB-independent pathway.

Conclusions:

• REV-ERB alpha/beta are crucial for maintaining cardiac fibroblasts in a quiescent state.
• Existing REV-ERB agonists may not be effective for cardiac fibrosis treatment due to their mechanism of action.
• Development of novel, REV-ERB-dependent agonists is necessary for targeting cardiac fibrosis.