Oral pathogen aggravates atherosclerosis by inducing smooth muscle cell apoptosis and repressing macrophage efferocytosis / 国际口腔科学杂志·英文版
International Journal of Oral Science
; (4): 26-26, 2023.
Article
in En
| WPRIM
| ID: wpr-982483
Responsible library:
WPRO
ABSTRACT
Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen, particularly the Porphyromonas gingivalis (P. gingivalis), by inducing apoptosis. However, it remains obscure whether accumulated apoptotic cells in P. gingivalis-accelerated plaque formation are associated with impaired macrophage clearance. Here, we show that smooth muscle cells (SMCs) have a greater susceptibility to P. gingivalis-induced apoptosis than endothelial cells through TLR2 pathway activation. Meanwhile, large amounts of miR-143/145 in P.gingivalis-infected SMCs are extracellularly released and captured by macrophages. Then, these miR-143/145 are translocated into the nucleus to promote Siglec-G transcription, which represses macrophage efferocytosis. By constructing three genetic mouse models, we further confirm the in vivo roles of TLR2 and miR-143/145 in P. gingivalis-accelerated atherosclerosis. Therapeutically, we develop P.gingivalis-pretreated macrophage membranes to coat metronidazole and anti-Siglec-G antibodies for treating atherosclerosis and periodontitis simultaneously. Our findings extend the knowledge of the mechanism and therapeutic strategy in oral pathogen-associated systemic diseases.
Full text:
1
Database:
WPRIM
Main subject:
Apoptosis
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Myocytes, Smooth Muscle
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MicroRNAs
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Endothelial Cells
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Atherosclerosis
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Toll-Like Receptor 2
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Macrophages
Limits:
Animals
Language:
En
Journal:
International Journal of Oral Science
Year:
2023
Document type:
Article