Lee Hansong, Joo Ji-Young, Kang Junho, Yu Yeuni, Kim Yun Hak, Park Hae Ryoun
Medical Research Institute, Pusan National University, Yangsan, Republic of Korea.
Department of Biomedical Informatics School of Medicine, Pusan National University, Yangsan, Republic of Korea.
Res Pract Thromb Haemost. 2023 Mar 7;7(2):100099. doi: 10.1016/j.rpth.2023.100099. eCollection 2023 Feb.
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.
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.
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.
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.
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.
已知血小板在动脉粥样硬化疾病、血栓形成和止血过程中发挥作用。对血小板转录组的研究可为增加心血管疾病易感性的疾病提供证据。然而,关于牙周炎患者以及牙周炎合并2型糖尿病(DM)患者血小板激活的分子机制研究仍很缺乏。
在本研究中,我们分析了牙周炎患者以及牙周炎合并DM患者血小板中的表达情况,以研究牙周炎诱导的血小板转录组特征以及DM的修饰作用。
我们采用单细胞RNA测序技术,获取了11名健康供者、10名牙周炎患者以及6名牙周炎合并DM患者的血小板转录谱。进一步探究了转录改变基因的生物学过程和共表达模块。
与健康个体相比,牙周炎合并DM患者以及单纯牙周炎患者的血小板激活和凝血信号水平均较高。牙周炎患者血小板中RHO GTPase效应器基因的表达水平较高,而牙周炎合并DM患者血小板中参与氧化磷酸化和细胞应激反应的基因表达高于对照组。然而,与单纯牙周炎患者相比,牙周炎合并DM患者的止血和血小板受体基因表达水平较低。
这些结果表明,牙周炎通过血小板失调促进凝血的发生,而牙周炎合并DM则损害血小板成分,从而影响其正常功能。