Periodontitis is closely linked to atherosclerosis; however, the role of the keystone periodontal pathogen Porphyromonas gingivalis (P. gingivalis), particularly its virulence factor, outer membrane vesicles (OMVs), in vascular smooth muscle cell (VSMC) dysfunction remains unclear. This study aimed to explore the effects of P. g-OMVs on mouse aortic smooth muscle cells (MOVAS) and the potential involvement of cytoskeleton-associated protein 4 (CKAP4) in this process. OMVs were isolated by ultracentrifugation and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. MOVAS cells were treated with OMVs; cellular functions were evaluated using CCK-8, colony formation, scratch wound-healing, ELISA, and Western blotting assays. Lentiviral vectors were used to construct CKAP4 overexpression and knockout cell models. Results showed that after P. g-OMVs were internalized by MOVAS cells, the cells showed cytoskeletal disorganization, promoting cell proliferation, wound closure, and contractile-to-synthetic phenotypic switching (decreased α-SMA and increased OPN expression), and enhancing extracellular matrix (ECM) remodeling (upregulated expression of type I collagen, type III collagen, fibronectin, matrix metalloproteinase-2 and -9, and tissue inhibitor of metalloproteinase-1). At the protein level, P. g-OMV treatment was associated with upregulated expression of CKAP4, integrin α5, and integrin β1; CKAP4 overexpression synergized with OMV stimulation to amplify these phenotypic alterations, whereas CKAP4 knockout attenuated these cellular changes. These findings suggest an association between CKAP4 upregulation and P. g-OMV-induced MOVAS dysfunction, indicating that CKAP4 may serve as a potential target in periodontitis-associated atherosclerosis.
Li et al. (Sun,) studied this question.