Yin-xing-tong-mai decoction attenuates atherosclerosis via activating PPARγ-LXRα-ABCA1/ABCG1 pathway

Area of Science:

• Cardiovascular Research
• Pharmacology
• Traditional Chinese Medicine

Background:

• Atherosclerosis, a leading cause of death, involves macrophage foam cell formation and impaired cholesterol efflux.
• The PPARγ-LXRα-ABCA1/ABCG1 pathway is crucial for cholesterol efflux but PPARγ agonist therapy faces challenges due to side effects.
• Traditional Chinese Medicine, like Yin-xing-tong-mai decoction (YXTMD), is used for atherosclerosis, yet its mechanism is unclear.

Purpose of the Study:

• To elucidate the mechanism by which YXTMD attenuates atherosclerosis.
• To investigate YXTMD's effect on cholesterol efflux and the PPARγ-LXRα-ABCA1/ABCG1 pathway in macrophages.

Main Methods:

• Utilized ApoE^-/- mice model to study YXTMD's effect on atherosclerosis in vivo.
• Performed in vitro experiments on foam cells to assess YXTMD's impact on cholesterol efflux.
• Employed bioinformatic analysis and experimental validation to identify YXTMD's molecular targets, focusing on PPARγ.

Main Results:

• YXTMD treatment significantly reduced atherosclerosis in ApoE^-/- mice.
• YXTMD enhanced cholesterol efflux from foam cells by upregulating ABCA1 and ABCG1 expression both in vivo and in vitro.
• PPARγ was identified as a key downstream target of YXTMD in macrophages, mediating the upregulation of LXRα, ABCA1, and ABCG1.

Conclusions:

• YXTMD effectively attenuates atherosclerosis.
• The therapeutic effect of YXTMD is attributed to the activation of the PPARγ-LXRα-ABCA1/ABCG1 pathway, which promotes cholesterol efflux.
• YXTMD presents a promising therapeutic agent for atherosclerosis by targeting cholesterol metabolism in macrophages.