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

• Published in: Molecular oral microbiology
• Main Authors: Tsai, Chien-Sung, Huang, Chun-Yao, Tsai, Yi-Ting, Shih, Chun-Ming, Lai, Ze-Hao, Liu, Chen-Wei, Lin, Yi-Wen, Lin, Feng-Yen
• Format: Journal Article
• Language: English
• Published: Denmark 04.02.2024
• Subjects: Porphyromonas gingivalis; orthotopic allograft transplantation; endothelials cells; vasculopathy
• ISSN: 2041-1006; 2041-1014
• DOI: 10.1111/omi.12453

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.