Transcriptomic Vascular and Endothelial Changes in Experimental Periodontitis in Nonhuman Primates.

Abstract

OBJECTIVE: The molecular features of the alterations in the integrity and function of the periodontal vasculature associated with the initiation/progression of periodontal lesions have not been well elucidated. METHODS: This study used a nonhuman primate model of experimental ligature-induced periodontitis across the lifespan to profile transcriptomic responses related to vasculature/endothelial cell biologic activities. RESULTS: In healthy tissues, genes representing EGF receptor signaling, VEGF signaling, and angiogenesis pathways showed some age effects. Disease initiation and/or early progression led to major changes in expression and a large number of vascular/endothelial genes showed correlations across the age groups. Specific bacteria (e.g., Veillonellacease, P. gingivalis, Fusobacterium) were highly correlated with gene changes (e.g., CCL2, CXCL1, EDN2, OCLN, PLAT, SELL, TGFB2). Overall differential expression analytics identified that the disease process appeared as the major controlling factor regarding the vascular/endothelial cell transcriptome. CONCLUSIONS: This study supports that alterations in vascular/endothelial cell biologic processes are observed in healthy tissues across the lifespan, with more substantive changes occurring during periodontal disease initiation and early progression. The expression patterns supported critical changes arising in the vasculature of gingival tissues that would contribute to the persistent nature of the immunoinflammatory response in this disease.