Systemic Endothelial Consequences of Periodontal Disease

牙周病的全身内皮后果

• 批准号: 7390399
• 负责人: Salomon Amar
• 金额: $ 50.28万
• 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 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7390399
• 关键词: Accounting; Acute-Phase Proteins; Affect; Aftercare; American; Atherosclerosis; Bacteremia; Bacterial Infections; Biological; Blood Vessels; Boston; C-reactive protein; Cardiovascular Diseases; Case-Control Studies; Cells; Chronic; Clinical; Clinical Trials; Conduct Clinical Trials; Cross-Sectional Studies; DNA; Dental Care; Dental Hygiene; Dental Schools; Dinoprostone; Disease; End Point; Endothelial Cells; Endothelium; Epidemiologic Studies; Framingham Heart Study; Functional disorder; Growth; Health; Homeostasis; Human; Individual; Inflammation; Inflammatory; Intercellular adhesion molecule 1; Interleukin-6; Intervention Studies; Intervention Trial; Laboratories; Lead; Left; Link; Measures; Mediating; Medical; Medicine; Nitric Oxide; Operative Surgical Procedures; Oral; Patients; Periodontal Diseases; Periodontal Infection; Periodontitis; Peroxidase; Pharmacology; Phenotype; Plasma; Play; Population; Process; Property; Protein C; Randomized; Recurrence; Regulation; Research Personnel; Resolution; Role; Root Scaling; Running; Source; Testing; Tooth structure; Universities; Vascular Endothelium; Vasodilator Agents; Vasomotor; Week; Work; alveolar bone; brachial artery; cardiovascular disorder risk; cardiovascular risk factor; cytokine; design; experience; follow-up; human subject; improved; insight; medical schools; novel strategies; oral biology; oral pathogen; pathogen; professor; scaling and root planing; soft tissue; therapy design

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。牙周病是牙龈的一种慢性细菌感染，与复发性菌血症和全身性炎症状态有关，这种炎症状态可能将内皮细胞转化为促动脉粥样硬化表型，炎症因子表达增加，内皮抗血栓、生长抑制和血管扩张特性丧失，包括一氧化氮生物活性降低。在人类受试者中，内皮功能障碍已经发展成为一个公认的早期动脉粥样硬化指标和心血管疾病风险增加的预测因子。我们最近在一项健康人类受试者的病例对照研究中证明了严重牙周病和内皮血管舒张功能障碍之间的强烈关联。在该研究中，牙周病也与血浆急性期反应物c反应蛋白（CRP）水平升高有关。这些结果支持了严重牙周病诱发系统性炎症损害内皮功能的假设，然而，横断面设计留下了混杂因素解释结果的可能性。我们现在提议在一项随机干预研究中确定牙周病的有效治疗是否能改善内皮功能（目的1）并减少炎症（目的2）。患者将接受全面的牙周治疗，以达到牙周健康状态（如有需要，进行牙周手术并进行牙根规划）或常规口腔卫生治疗，并随访24周。该研究将检查治疗前后内皮依赖性肱动脉血流介导的扩张、炎症和内皮活化的全身标志物（CRP、IL-6、髓过氧化物酶和ICAM-1）以及牙周炎的口腔标志物（PGE2、髓过氧化物酶和病原体DNA）。与口腔卫生（可以稳定牙周病，但不能逆转牙周病）相比，我们假设牙周病的综合治疗可以改善内皮依赖性扩张，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特定炎症标志物的减少程度有关。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关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。