Porphyromonas Gingivalis Synergizes With Vascular Smooth Muscle Cells Exacerbating Atherosclerosis

To investigate whether Porphyromonas gingivalis (Pg) in a comorbid rat model drives vascular smooth muscle cells (VSMCs) phenotypic switching, mediates pathological vascular remodeling, and accelerates atherosclerosis. Ethics-approved protocols were applied to 6-week-old male SD rats (n=28) with comorbid atherosclerosis and periodontitis. Alveolar bone resorption was quantified by micro-CT. Atheroscleric plaques were analyzed for lipid deposition (Oil Red O) and collagen fiber organization (histopathology). MMP-2/9 levels in serum were measured by ELISA. In human aortic VSMCs, Pg (MOI=20-500) induced phenotypic switching (SM22α, OPN via WB/qPCR), cytoskeletal (immunofluorescence), and organelle structure (TEM). Investigate the role of bioinformatics analysis identified ETS-1 knockdown/overexpression. Pg-infected rats exhibited aggravated atherosclerosis (p<0.05) with enhanced VSMC phenotypic switching (SM22α reduced, OPN elevated) and exacerbated pathological vascular remodeling. In VSMCs, Pg activated ETS-1 to drive phenotypic switching, cytoskeletal rearrangement, and organelle structural damage. Genetic inhibition of ETS-1 significantly attenuated Pg-induced VSMCs phenotypic switching. This study provides the first in vivo evidence in a comorbid rat model that Pg exploits ETS-1 to induce VSMC phenotypic switching, mediate pathological vascular remodeling, and promote atherosclerosis. By linking oral infection to vascular pathology through VSMCs, our findings highlight that therapeutic potential in modulating VSMCs function, and the critical role of ETS-1 in disrupting the oral-cardiovascular axis.