PLASMINOGEN ACTIVATORS IN PERIODONTITIS AND DIABETES

牙周炎和糖尿病中的纤溶酶原激活剂

• 批准号: 6652570
• 负责人: ARTHUR A DECARLO
• 金额: $ 13.37万
• 依托单位: NOVA SOUTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6652570
• 关键词: collagen; collagenase; diabetes mellitus; diabetic angiopathy; diabetic retinopathy; enzyme activity; epithelium; extracellular matrix proteins; gene expression; genetic polymorphism; genotype; gingiva; histopathology; human tissue; laminin; messenger RNA; molecular pathology; mucosa; periodontitis; plasminogen activator; plasminogen activator inhibitors; protein degradation; tissue /cell culture; vascular endothelium; western blottings

Periodontal disease in individuals with diabetes mellitus is more frequent and more severe. Both periodontitis and diabetes patients present with extracellular matrix changes associated with the microvasculature. We propose that changes in the microvasculature are a common, fundamental process in the development of tissue pathology in both Adult Periodontitis and diabetes mellitus, and we offer this as an explanation for the increased incidence and severity of periodontitis in diabetics. Because the plasminogen activators (PA) and their inhibitors, plasminogen activator inhibitors (PAIs) are known to have a critical role in angiogenesis and angiopathies, as well as in extracellular remodeling and fibrinolysis, we propose to demonstrate a significant association of the Pas and PAIs with both periodontitis and diabetes severity, and to show that the exacerbation of periodontitis in diabetics is a function of Pas and PAIs. Diabetes-associated pathology will be measured as the level of diabetic retinopathy, previously demonstrated to correlate with periodontitis severity. Gingival microvasculature changes will be measured by morphometric analysis of histologic sections. We will measure Pas and PAIs in three different ways: genotypes, cellular response levels, and in vivo tissue levels. Our hypothesis states that POA/PAI parameters will be similarly associated with measurements of periodontitis and diabetes pathology but significantly different from levels found in healthy control participants. To address pathophysiology mechanisms which would link changes in PAs and PAIs in three different ways: genotypes, cellular response levels, and in vivo tissue levels. Our hypothesis states that PA/PAI parameters will be similarly associated with control participants. To address pathophysiological mechanisms which would link changes in PAs and PAIs with development of microangiopathy we will use an in vitro endothelial cell microvessel assay system, expression and activation of matrix metalloproteinases, and accumulation of matrix proteins such as type IV collagen and laminin. Anticipated results may focus the targeting of therapeutic intervention for pathology associated with periodontal disease and diabetes mellitus towards the Pas and PAIs and may allow earlier intervention for a patient population determined genotypically to be at risk.

糖尿病患者的牙周病更常见，也更严重。牙周炎和糖尿病患者都表现出与微血管有关的细胞外基质改变。我们认为，微血管的改变是成人牙周炎和糖尿病组织病理学发展过程中常见的、基本的过程，这是糖尿病患者牙周炎发病率和严重性增加的原因。由于纤溶酶原激活物(PA)及其抑制物(PAI)在血管生成和血管病变以及细胞外重构和纤溶中起关键作用，我们建议证明PAS和PAI与牙周炎和糖尿病严重程度显著相关，并表明糖尿病患者牙周炎的恶化是PAS和PAIS的作用。糖尿病相关的病理将被测量为糖尿病视网膜病变的水平，以前被证明与牙周炎的严重程度相关。牙周微血管改变将通过组织切片的形态计量学分析来测量。我们将通过三种不同的方法测量PAS和PAI：基因类型、细胞反应水平和体内组织水平。我们的假设表明，POA/PAI参数将与牙周炎和糖尿病病理的测量类似，但与健康对照组参与者的水平明显不同。以三种不同的方式阐述PAS和PAI变化的病理生理学机制：基因类型、细胞反应水平和体内组织水平。我们的假设表明，PA/PAI参数将类似地与对照组参与者相关。为了解决PAS和PAI的变化与微血管病变发展之间的联系的病理生理机制，我们将使用体外内皮细胞微血管检测系统，研究基质金属蛋白酶的表达和激活，以及基质蛋白的积聚，如IV型胶原和层粘连蛋白。预期结果可能会将针对牙周病和糖尿病相关病理的治疗干预集中在PAS和PAI上，并可能允许对被确定为基因风险的患者群体进行更早的干预。