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Geniposide Enhances Macrophage Autophagy through Downregulation of TREM2 in Atherosclerosis

Authors :
Xiaoyu Liu
Yuhua Jia
Feng-hua Zhou
Mu-Keng Hong
Yuyao Chen
Pei-Kun He
Yu-Ling Xu
Saibo Cheng
Source :
The American journal of Chinese medicine. 48(8)
Publication Year :
2020

Abstract

Macrophage autophagy defect is closely related to the progression of atherosclerosis (AS) and is regulated by the triggering receptor expressed on myeloid cell 2 (TREM2). TREM2 is a key factor in the development of Alzheimer’s disease (AD), the deficiency of which leads to anomalous autophagy in microglia. However, the role of TREM2 in the autophagy of plaque macrophages is still unclear. Geniposide (GP) can inhibit AS progression and enhance macrophage autophagy, although the underlying mechanisms remain unknown. We found that high-fat diet (HFD) feeding significantly increased TREM2 levels and inhibited autophagy in the macrophages of ApoE[Formula: see text] mice. TREM2 overexpression in RAW264.7 macrophages decreased autophagy via activation of mTOR signaling. GP inhibited the progression of AS in ApoE[Formula: see text] mice, reinforced macrophage autophagy, and downregulated TREM2 by inhibiting mTOR signaling. Taken together, augmenting the autophagy levels in plaque macrophages by inhibiting the TREM2/mTOR axis can potentially impede atherosclerotic progression. The promising therapeutic effects of GP seen in this study should be validated in future trials, and the underlying mechanisms have to be elucidated in greater detail.

Details

ISSN :
17936853
Volume :
48
Issue :
8
Database :
OpenAIRE
Journal :
The American journal of Chinese medicine
Accession number :
edsair.doi.dedup.....484733e6e59013c97e4bf691e2b2053b