Endothelial CD36 mediates Porphyromonas gingivalis-induced insulin resistance and vascular aging via mitochondrial dysfunction.

Periodontitis is increasingly recognized as a critical systemic risk factor that exacerbates insulin resistance (IR) and subsequently accelerates vascular aging. As the keystone periodontal pathogen, Porphyromonas gingivalis (Pg) is known to drive these systemic metabolic disruptions, yet the precise mechanisms linking infection to vascular aging remain poorly understood. Here, we investigate the pivotal role of the endothelial CD36 receptor in mediating Pg -induced IR and vascular aging. Utilizing murine and primary endothelial cell models, this study demonstrates that Pg infection induces systemic glucose intolerance, suppresses canonical insulin signaling, and triggers profound endothelial dysfunction characterized by inflammation, apoptosis and impaired angiogenesis. Crucially, targeted endothelial knockout of CD36 (EC CD36 KO) effectively mitigated these pathogen-induced pathological outcomes, rescuing systemic glucose homeostasis and restoring endothelial function. Mechanistically, this Pg-induced aging phenotype was driven by hyperactivation of the Angiotensin II (Ang II) signaling axis and severe mitochondrial dysfunction. Correspondingly, the deficiency of endothelial CD36 restrained Ang II-driven oxidative stress and prevented mitochondrial damage. Taken together, these findings establish endothelial CD36 as a fundamental mechanistic node linking periodontal infection to metabolic dysregulation. This provides a compelling molecular rationale for targeting endothelial CD36 to attenuate periodontitis-exacerbated IR and premature vascular aging.