Systemic Endothelial Consequences of Periodontal Disease

牙周病的全身内皮后果

• 批准号: 6885796
• 负责人: Salomon Amar
• 金额: $ 50.7万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6885796
• 关键词: acute phase protein; bacterial DNA; blood chemistry; blood flow measurement; cardiovascular disorder prevention; cardiovascular disorder risk; cell adhesion molecules; clinical trials; dental plaque; human subject; human therapy evaluation; interleukin 6; interview; medical complication; microorganism growth; myeloperoxidase; nucleic acid quantitation /detection; oral bacteria; oral pharyngeal surgery; patient oriented research; periodontitis; periodontium disorder; preventive dentistry; ultrasonography; vascular endothelium

DESCRIPTION (provided by applicant): Epidemiological studies indicate that individuals with severe periodontal disease have significantly increased risk for cardiovascular disease. Periodontal disease, a chronic bacterial infection of the gums, is associated with recurrent bacteremia and a state of systemic inflammation that may convert endothelial cells to a pro-atherogenic phenotype with increased expression of inflammatory factors and loss of the anti-thrombotic, growth inhibitory, and vasodilator properties of the endothelium, including a decrease in the biological activity of nitric oxide. In human subjects, endothelial dysfunction has evolved into a well accepted indicator of early atherosclerosis and predictor of increased cardiovascular disease risk. We have recently demonstrated a strong association between severe periodontal disease and endothelial vasomotor dysfunction in a case control study of otherwise healthy human subjects. In that study, periodontal disease was also associated with higher plasma levels of the acute phase reactant C-reactive protein (CRP). These results support the hypothesis that severe periodontal disease induces a state of systemic inflammation that impairs endothelial function, however, the cross-sectional design leaves open the possibility that confounding factors explain the results. We now propose to determine whether effective treatment of periodontal disease improves endothelial function (Aim 1) and reduces inflammation (Aim 2) in a randomized intervention study. Patients will receive comprehensive periodontal treatment designed to produce a state of periodontal health (scaling and root planning and periodontal surgery with re-treatment as needed) or routine oral hygiene and will be followed for 24 weeks. The study will examine endothelium-dependent brachial artery flow-mediated dilation, systemic markers of inflammation and endothelial activation (CRP, IL-6, myeloperoxidase, and ICAM-1), and oral markers of periodontitis (PGE2, myeloperoxidase, and pathogen DNA) before and after treatment. Compared to oral hygiene (which will stabilize, but not reverse periodontal disease), we hypothesize that comprehensive treatment of periodontal disease will improve endothelium-dependent dilation and reduce local and systemic inflammation. Further, we suggest that the degree of improvement in endothelial function will relate to the degree of reduction in specific markers of inflammation. Such results would provide much stronger evidence for causal links between periodontal disease, systemic inflammation, and endothelial dysfunction, a recognized surrogate for cardiovascular risk. The proposed studies will provide new insights into how periodontal disease contributes to cardiovascular disease risk in human subjects and may lead to new approaches to therapy.

描述(由申请人提供)：流行病学研究表明，患有严重牙周病的人患心血管疾病的风险显著增加。牙周病是牙周的一种慢性细菌感染，与反复的菌血症和全身炎症状态有关，这种炎症状态可能会使内皮细胞转化为促动脉粥样硬化的表型，炎症因子的表达增加，内皮细胞的抗血栓、生长抑制和血管扩张特性丧失，包括一氧化氮生物活性的降低。在人类受试者中，内皮功能障碍已演变为公认的早期动脉粥样硬化的指标和心血管疾病风险增加的预测因子。我们最近在一项病例对照研究中证明，严重的牙周病与内皮血管运动功能障碍之间存在很强的相关性。在这项研究中，牙周病也与急性期反应物C反应蛋白(CRP)的血浆水平较高有关。这些结果支持这样的假设，即严重的牙周病会导致全身炎症状态，从而损害内皮功能，然而，横断面设计保留了混杂因素解释结果的可能性。我们现在建议在一项随机干预研究中确定有效的牙周病治疗是否能改善内皮功能(目标1)和减少炎症(目标2)。患者将接受全面的牙周治疗，以达到牙周健康的状态(根据需要进行牙周刮除和牙根规划和牙周手术，并根据需要重新治疗)或常规的口腔卫生，并将跟踪观察24周。这项研究将检测治疗前后的内皮依赖性肱动脉血流介导的扩张、炎症和内皮激活的系统标志物(CRP、IL-6、髓过氧化物酶和ICAM-1)以及牙周炎的口服标志物(PGE2、髓过氧化物酶和病原体DNA)。与口腔卫生(将稳定牙周病，但不能逆转牙周病)相比，我们假设牙周病的综合治疗将改善内皮依赖性扩张，并减少局部和全身炎症。此外，我们认为内皮功能的改善程度将与炎症的特定标记物的减少程度有关。这些结果将为牙周病、全身性炎症和内皮功能障碍之间的因果联系提供更有力的证据，内皮功能障碍是公认的心血管风险的替代指标。拟议的研究将为牙周病如何导致人类心血管疾病风险提供新的见解，并可能导致新的治疗方法。