Porphyromonas Gingivalis Triggers Ferroptosis In Vascular Endothelial Cells

Porphyromonas gingivalis (P. gingivalis) can enter cardiovascular system to cause endothelial death, which is critical for cardiovascular health. Ferroptosis is a potential target for cardiovascular diseases prevention and treatment. Whether P. gingivalis is involved in ferroptosis regulation in vascular endothelial cells is unknown. Therefore, this study aimed to investigate whether P. gingivalis induces ferroptosis in vascular endothelial cells and identify relative target genes. Firstly, transcriptome sequencing was conducted on human umbilical vein endothelial cells (HUVECs) before and after P. gingivalis stimulation, and ferroptosis-related genes were screened. Subsequently, the Cytoscape software and STRING and GeneMANIA databases were utilized to identify the key regulatory genes of ferroptosis. Finally, molecular biology techniques were employed to validate the effects of P. gingivalis on ferroptosis in HUVECs and to assess the expression of the key ferroptosis-related regulatory genes . Transcriptome sequencing revealed that P. gingivalis led to a significant change in the transcriptional profile of HUVECs and induced ferroptosis, and the key ferroptosis-related regulatory genes included tumor necrosis factor (TNF), interleukin 6 (IL6), and prostaglandin-endoperoxide synthase 2 (PTGS2). In vitro cell validation experiments showed that P. gingivalis lipopolysaccharide(LPS)triggered ferroptosis of HUVECs through mechanisms involving lipid peroxidation, Fe2+ accumulation, glutathione biosynthesis suppression, and so on. Besides, P. gingivalis-LPS was demonstrated to upregulate TNF, IL6, and PTGS2 expression. P. gingivalis regulated ferroptosis in HUVECs, with TNF, IL6, and PTGS2 being the targets for further exploration, which is helpful for revealing new therapeutic inspiration for endothelial health from the perspective of periodontics.