Oral pathogen aggravates atherosclerosis by inducing smooth muscle cell apoptosis and repressing macrophage efferocytosis.
10.1038/s41368-023-00232-5
- Author:
Hanyu XIE
1
;
Ziyue QIN
2
;
Ziji LING
1
;
Xiao GE
1
;
Hang ZHANG
1
;
Shuyu GUO
2
;
Laikui LIU
2
;
Kai ZHENG
2
;
Hongbing JIANG
3
;
Rongyao XU
4
Author Information
1. Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
2. Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
3. Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China. jhb@njmu.edu.cn.
4. Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China. rongyaoxu@njmu.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- MeSH:
Animals;
Mice;
Endothelial Cells;
Toll-Like Receptor 2;
Macrophages;
Apoptosis;
Atherosclerosis;
Myocytes, Smooth Muscle;
MicroRNAs
- From:
International Journal of Oral Science
2023;15(1):26-26
- CountryChina
- Language:English
-
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.