Activating PPARα in macrophages attenuates arterial remodeling via inhibiting YAP nuclear localization

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Inflammation Research

Background:

• Arterial remodeling contributes significantly to cardiovascular morbidity and mortality.
• Adventitial inflammation is a critical factor in pathological arterial remodeling, but its molecular drivers are not fully understood.

Purpose of the Study:

• To investigate the role and mechanism of peroxisome proliferator-activated receptor alpha (PPARα) in arterial remodeling.
• To explore PPARα's potential as a therapeutic target for cardiovascular conditions.

Main Methods:

• Utilized the transverse aortic constriction (TAC) model to induce pressure-overload arterial remodeling.
• Administered a PPARα agonist (Wy14643) and assessed its effects on arterial remodeling and adventitial inflammation.
• Investigated the interaction between PPARα and yes-associated protein (YAP) signaling pathways in macrophages.

Main Results:

• TAC model showed decreased PPARα expression in adventitial macrophages.
• Wy14643 treatment ameliorated arterial remodeling, particularly adventitial changes.
• PPARα activation inhibited YAP nuclear translocation, reducing macrophage infiltration and M1 polarization.
• YAP signaling blockade also suppressed pathological arterial alterations.

Conclusions:

• PPARα activation mitigates arterial remodeling by modulating macrophage behavior via YAP signaling.
• PPARα represents a promising therapeutic target for treating arterial remodeling and associated cardiovascular diseases.