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.

中文翻译：

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牙龈卟啉单胞菌 GroEL 通过损害内皮细胞功能加剧原位同种异体移植血管病变

同种异体原位移植（OAT）是解决器官衰竭的重要方法。然而，对同种异体移植物的持续免疫反应会影响慢性排斥反应，从而诱发 OAT 血管病变 (OATV) 和器官衰竭。牙龈卟啉单胞菌可以通过血流渗透到远端器官，从而加剧心血管、呼吸系统、神经退行性疾病和癌症的严重程度。 GroEL 是牙龈卟啉单胞菌的毒力因子，可促进宿主细胞中促炎细胞因子的产生，这在心血管疾病的发病机制中发挥着关键作用。尽管 OATV 的恶化可归因于多种因素，但 GroEL 的作用仍然不明确。因此，本研究旨在探讨 GroEL 对 OATV 的影响。从PVG/Seac大鼠中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 通过影响 EPC 和平滑肌祖细胞 (SMPC) 功能并促进胶原蛋白的异常积累，加剧 ACI/NKyo 大鼠的 OATV。在体外，GroEL 刺激 EPC 中的内皮-间质转化，通过下调连接蛋白来减少 HCAEC 管形成和屏障功能，通过降低线粒体膜电位和呼吸功能来加速 HCAEC 老化，并通过调节细胞骨架相关分子来阻止 HCAEC 迁移。这项研究表明，牙龈卟啉单胞菌GroEL 可能通过影响血管祖细胞和内皮细胞功能来增强 OATV。