牙周炎通过DAGK调控ERK1/2-NF-κB信号通路加重心肌梗死的机制研究

The exacerbation of myocardial infarction by periodontitis involves DAGK-mediated modulation of the ERK1/2-NF-κB signaling pathway

摘要

目的 探讨牙周炎与心肌梗死之间是否存在因果关系,揭示其潜在的分子机制。方法 采用双样本孟德尔随机化分析评估牙周炎与心肌梗死的因果关系,并结合生物信息学分析筛选潜在靶点。通过建立动物模型,利用micro-CT、组织学染色、免疫荧光染色、超声心动图及心电图等技术进行体内实验验证。结果 孟德尔随机化分析结果显示,牙周炎与心肌梗死风险呈显著正相关。机制研究表明,牙周炎通过二酰基甘油激酶介导的细胞外信号调节激酶1/2-核因子-κB(ERK1/2-NF-κB)信号通路被激活,加重心肌梗死后的病理损伤。结论 牙周炎是心肌梗死的风险因素,其机制可能与二酰基甘油激酶调控的ERK1/2-NF-κB信号通路有关。该发现为改善伴牙周炎的心肌梗死患者预后及减少不良心室重构提供有效策略。

Abstract

Objective To investigate the causal relationship between periodontitis and myocardial infarction and to elucidate the underlying molecular mechanisms. Methods A two-sample Mendelian randomization analysis was employed to assess the causal association between periodontitis and myocardial infarction, combined with bioinformatics analysis to screen for potential therapeutic targets. In vivo validation was conducted using established animal models, utilizing techniques such as micro-CT, histological staining, immunofluorescence staining, echocardiography, and electrocardiography. Results The Mendelian randomization analysis demonstrated a significant positive correlation between periodontitis and the risk of myocardial infarction. Mechanistic investigations revealed that periodontitis exacerbates post-myocardial infarction pathological injury via the activation of the diacylglycerol kinase-mediated extracellular signal-regulated kinase1/2-nuclear factor κB(ERK1/2-NF-κB)signaling pathway. Conclusion Periodontitis serves as a risk factor for myocardial infarction, with mechanisms potentially involving the diacylglycerol kinase-regulated ERK1/2-NF-κB signaling pathway. These findings provide effective strategies for improving the prognosis of myocardial infarction patients with comorbid periodontitis and mitigating adverse ventricular remodeling.

关键词

牙周炎 / 心肌梗死 / 孟德尔随机化分析 / 生信分析 / 细胞外信号调节激酶1/2-核因子-κB信号通路

Key words

Periodontitis / Myocardial infarction / Mendelian randomization analysis / Bioinformatics analysis / Extracellular signal-regulated kinase1/2-nuclear factor kappa-B signaling pathway

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