期刊
AMERICAN JOURNAL OF CHINESE MEDICINE
卷 48, 期 8, 页码 1821-1840出版社
WORLD SCIENTIFIC PUBL CO PTE LTD
DOI: 10.1142/S0192415X20500913
关键词
Macrophage Autophagy; TREM2; Atherosclerosis; Geniposide; mTOR Signaling
资金
- National Natural Sciences Foundation of China [81373574, 81973802]
- Science and Technology Planning Project of Guangdong Province, China [2016A020226002]
- Secondary development Project of Famous and Excellent Chinese Patent Medicine of Guangdong, China [20174010]
- Guangzhou Municipal Science and Technology Project, China [201704020042]
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(-/-) mice. TREM2 overexpression in RAW264.7 macrophages decreased autophagy via activation of mTOR signaling. GP inhibited the progression of AS in ApoE(-/-) 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.
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