口腔病原体通过诱导平滑肌细胞凋亡和抑制巨噬细胞efferocysis而加重动脉粥样硬化。

IF 10.8 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE International Journal of Oral Science Pub Date : 2023-06-28 DOI:10.1038/s41368-023-00232-5
Hanyu Xie, Ziyue Qin, Ziji Ling, Xiao Ge, Hang Zhang, Shuyu Guo, Laikui Liu, Kai Zheng, Hongbing Jiang, Rongyao Xu
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引用次数: 0

摘要

牙周炎增加动脉粥样硬化性心血管疾病的风险部分是由于口腔病原体,特别是牙龈卟啉单胞菌(P. gingivalis),通过诱导细胞凋亡的免疫颠覆。然而,目前尚不清楚牙龈假单胞菌加速斑块形成中积累的凋亡细胞是否与巨噬细胞清除受损有关。在这里,我们发现通过TLR2通路激活,平滑肌细胞(SMCs)比内皮细胞更容易受到牙龈假单胞菌诱导的凋亡。同时,大量的miR-143/145在牙龈假单胞菌感染的SMCs中被细胞外释放并被巨噬细胞捕获。然后,这些miR-143/145被易位到细胞核中,促进siglecg转录,从而抑制巨噬细胞的efferocytosis。通过构建三种小鼠遗传模型,我们进一步证实了TLR2和miR-143/145在牙龈卟卟酸加速动脉粥样硬化中的体内作用。在治疗方面,我们开发了牙龈卟啉预处理的巨噬细胞膜,以包裹甲硝唑和抗siglecg抗体,同时治疗动脉粥样硬化和牙周炎。我们的发现扩展了对口腔病原体相关全身性疾病的机制和治疗策略的认识。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Oral pathogen aggravates atherosclerosis by inducing smooth muscle cell apoptosis and repressing macrophage efferocytosis.

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.

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来源期刊
International Journal of Oral Science
International Journal of Oral Science DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
31.80
自引率
1.30%
发文量
53
审稿时长
>12 weeks
期刊介绍: The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to: Oral microbiology Oral and maxillofacial oncology Cariology Oral inflammation and infection Dental stem cells and regenerative medicine Craniofacial surgery Dental material Oral biomechanics Oral, dental, and maxillofacial genetic and developmental diseases Craniofacial bone research Craniofacial-related biomaterials Temporomandibular joint disorder and osteoarthritis The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.
期刊最新文献
Organoids in the oral and maxillofacial region: present and future. Personalized bioceramic grafts for craniomaxillofacial bone regeneration An unexpected role of neurite outgrowth inhibitor A as regulator of tooth enamel formation Periodontitis impacts on thrombotic diseases: from clinical aspect to future therapeutic approaches. CREB3L1 deficiency impairs odontoblastic differentiation and molar dentin deposition partially through the TMEM30B.
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