Epoxyeicosatrienoic acids regulate macrophage polarization and prevent LPS-induced cardiac dysfunction

Area of Science:

• Cardiovascular Research
• Immunology
• Molecular Biology

Background:

• Macrophages exhibit plasticity and are key players in inflammatory, metabolic, and immune diseases.
• Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acid to epoxyeicosatrienoic acids (EETs), known for cardiovascular benefits.

Purpose of the Study:

• To evaluate EETs' effects on macrophage polarization.
• To assess recombinant adeno-associated virus (rAAV)-mediated CYP2J2 expression in lipopolysaccharide (LPS)-induced cardiac dysfunction.
• To investigate the underlying mechanisms of these effects.

Main Methods:

• In vitro studies using EETs on LPS-stimulated macrophages.
• In vivo studies using rAAV-mediated CYP2J2 expression in LPS-treated mice.
• Analysis of macrophage polarization markers, cytokine levels, and signaling pathways (NF-κB, PPARα/γ, HO-1).

Main Results:

• EETs inhibited M1 macrophage polarization and pro-inflammatory cytokines while promoting M2 markers and IL-10.
• EETs downregulated NF-κB activation and upregulated PPARα/γ and HO-1.
• rAAV-mediated CYP2J2 expression in mice attenuated LPS-induced cardiac dysfunction, heart damage, and inflammation, mirroring in vitro findings.

Conclusions:

• CYP2J2/EETs regulate macrophage polarization by modulating the NF-κB signaling pathway through PPARα/γ and HO-1 activation.
• This pathway offers potential therapeutic strategies for inflammatory diseases, particularly those involving cardiac dysfunction.