Porphyromonas gingivalis GroEL exacerbates orthotopic allograft transplantation vasculopathy via impairment of endothelial cell function.

IF 2.8 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Molecular Oral Microbiology Pub Date : 2024-02-04 DOI:10.1111/omi.12453

Chien-Sung Tsai, Chun-Yao Huang, Yi-Ting Tsai, Chun-Ming Shih, Ze-Hao Lai, Chen-Wei Liu, Yi-Wen Lin, Feng-Yen Lin

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引用次数: 0

Abstract

Orthotopic allograft transplantation (OAT) is a significant approach to addressing organ failure. However, persistent immune responses to the allograft affect chronic rejection, which induces OAT vasculopathy (OATV) and organ failure. Porphyromonas gingivalis can infiltrate remote organs via the bloodstream, thereby intensifying the severity of cardiovascular, respiratory, and neurodegenerative diseases and cancer. GroEL, a virulence factor of P. gingivalis promotes pro-inflammatory cytokine production in host cells, which assumes to play a pivotal role in the pathogenesis of cardiovascular diseases. Although the aggravation of OATV is attributable to numerous factors, the role of GroEL remains ambiguous. Therefore, this study aimed to investigate the impact of GroEL on OATV. Aortic grafts extracted from PVG/Seac rats were transplanted into ACI/NKyo rats and in vitro human endothelial progenitor cell (EPC) and coronary artery endothelial cell (HCAEC) models. The experimental findings revealed that GroEL exacerbates OATV in ACI/NKyo rats by affecting EPC and smooth muscle progenitor cell (SMPC) function and enabling the anomalous accumulation of collagen. In vitro, GroEL spurs endothelial-mesenchymal transition in EPCs, reduces HCAEC tube formation and barrier function by downregulating junction proteins, accelerates HCAEC aging by lowering mitochondrial membrane potential and respiratory function, and impedes HCAEC migration by modulating cytoskeleton-associated molecules. This study suggests that P. gingivalis GroEL could potentially augment OATV by impacting vascular progenitor and endothelial cell functions.

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牙龈卟啉菌 GroEL 通过损害内皮细胞功能加剧同种异体移植血管病变。

同种异位移植（OAT）是解决器官衰竭的重要方法。然而，对异体移植的持续免疫反应会影响慢性排斥反应，从而诱发异体移植血管病变（OATV）和器官衰竭。牙龈卟啉单胞菌可通过血液浸润远处器官，从而加剧心血管、呼吸、神经退行性疾病和癌症的严重程度。牙龈脓胞杆菌的毒力因子 GroEL 可促进宿主细胞产生促炎细胞因子，这在心血管疾病的发病机制中起着关键作用。虽然 OATV 的恶化可归因于多种因素，但 GroEL 的作用仍不明确。因此，本研究旨在探讨 GroEL 对 OATV 的影响。将从 PVG/Seac 大鼠身上提取的主动脉移植物移植到 ACI/NKyo 大鼠和体外人内皮祖细胞（EPC）和冠状动脉内皮细胞（HCAEC）模型中。实验结果表明，GroEL会影响EPC和平滑肌祖细胞（SMPC）的功能，使胶原蛋白异常积聚，从而加剧ACI/NKyo大鼠的OATV。在体外，GroEL会刺激EPC的内皮-间质转化，通过下调连接蛋白减少HCAEC管形成和屏障功能，通过降低线粒体膜电位和呼吸功能加速HCAEC衰老，以及通过调节细胞骨架相关分子阻碍HCAEC迁移。这项研究表明，P. gingivalis GroEL 有可能通过影响血管祖细胞和内皮细胞的功能来增强 OATV。

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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来源期刊

Molecular Oral Microbiology DENTISTRY, ORAL SURGERY & MEDICINE-MICROBIOLOGY

CiteScore

6.50

自引率

5.40%

发文量

审稿时长

>12 weeks

期刊介绍： Molecular Oral Microbiology publishes high quality research papers and reviews on fundamental or applied molecular studies of microorganisms of the oral cavity and respiratory tract, host-microbe interactions, cellular microbiology, molecular ecology, and immunological studies of oral and respiratory tract infections. Papers describing work in virology, or in immunology unrelated to microbial colonization or infection, will not be acceptable. Studies of the prevalence of organisms or of antimicrobials agents also are not within the scope of the journal. The journal does not publish Short Communications or Letters to the Editor. Molecular Oral Microbiology is published bimonthly.