Single-cell analysis of platelets from patients with periodontitis and diabetes.

ABSTRACT

Background: Blood platelets are known to play a role in the development of atherosclerotic disease, thrombi, and hemostasis. Investigation of blood platelet transcriptome could provide evidence of disorders that increase vulnerability to cardiovascular disease. However, research on the molecular insights of platelet activation in patients with periodontitis and patients with periodontitis and type 2 diabetes mellitus (DM) is still lacking. Objectives: In this study, we analyzed expression in blood platelets from patients with periodontitis and patients with concurrent periodontitis and DM to examine the transcriptomic profile of platelets induced by periodontitis and the modifying effects of DM. Methods: We obtained the transcriptional profiles of blood platelets from 11 healthy donors, 10 patients with periodontitis, and 6 patients with periodontitis and DM using single-cell RNA sequencing. The biological processes and coexpressed modules of transcriptionally altered genes were further explored. Results: Both the patients with periodontitis and DM and those with periodontitis without DM showed higher levels of platelet activation and coagulation signals than the healthy individuals. Platelets from the patients with periodontitis had higher expression levels of genes for RHO GTPase effectors, whereas platelets from the patients with periodontitis and DM demonstrated higher expression of genes involved in oxidative phosphorylation and cellular responses to stress than those from the controls. However, compared with the patients with only periodontitis, those with periodontitis and DM presented a lower expression level of genes for hemostasis and platelet receptors. Conclusion: These results suggest that periodontitis contributes to establishment of blood coagulation via platelet dysregulation, whereas the comorbidities of patients with periodontitis and DM impair the components of platelets, thus preventing normal functions.