MaiJiTong granule attenuates atherosclerosis by reducing ferroptosis via activating STAT6-mediated inhibition of DMT1...

Area of Science:

• Cardiovascular Disease Research
• Cell Death Mechanisms
• Traditional Chinese Medicine

Background:

• Atherosclerosis, a major cause of cardiovascular disease, is promoted by ferroptosis, an iron-driven cell death process.
• STAT6's role in ferroptosis during atherogenesis is unclear.
• Maijitong granule (MJT), a Traditional Chinese Medicine, may inhibit ferroptosis and treat atherosclerosis, but its mechanism is unknown.

Purpose of the Study:

• To determine STAT6's role in ferroptosis during atherogenesis.
• To investigate MJT's anti-atherosclerotic effects.
• To ascertain if MJT's effects are mediated by ferroptosis inhibition.

Main Methods:

• Utilized low-density lipoprotein receptor-deficient (LDLR-/-) mice fed a high-fat diet (HFD) to assess MJT's preventive and therapeutic effects.
• Evaluated gene expression related to lipid peroxidation and iron metabolism to understand MJT's anti-ferroptotic mechanisms.
• Analyzed microarray data (GSE28117) for STAT6-ferroptosis correlation and used STAT6 knockout mice to validate findings.

Main Results:

• MJT attenuated atherosclerosis, reduced plaque size, and enhanced stability.
• MJT inhibited inflammation and foam cell formation by modulating lipid metabolism.
• STAT6 negatively regulated ferroptosis by suppressing SOCS1/p53 and DMT1; MJT activated STAT6 phosphorylation, inhibiting these pathways.

Conclusions:

• STAT6 acts as a negative regulator of ferroptosis and atherosclerosis by suppressing DMT1 and SOCS1/p53.
• MJT attenuates atherosclerosis and ferroptosis by activating STAT6-mediated inhibition of DMT1 and SOCS1/p53.
• STAT6 is a promising therapeutic target for atherosclerosis, and MJT offers a potential new treatment.