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: 6095206
• 负责人: ARTHUR A DECARLO
• 金额: $ 20.85万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 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 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6095206
• 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.

牙周病在糖尿病患者中更为常见和严重。牙周炎和糖尿病患者均存在与微血管相关的细胞外基质改变。我们认为，在成人牙周炎和糖尿病的组织病理发展中，微血管的改变是一个共同的、基本的过程，我们提出这可以解释糖尿病患者牙周炎发病率和严重程度增加的原因。由于已知纤溶酶原激活剂（PA）及其抑制剂，纤溶酶原激活剂抑制剂（PAIs）在血管生成和血管病变，以及细胞外重塑和纤维蛋白溶解中具有关键作用，我们提出证明Pas和PAIs与牙周炎和糖尿病严重程度的显著关联，并表明糖尿病患者牙周炎的恶化是Pas和PAIs的功能。糖尿病相关病理将被测量为糖尿病视网膜病变的水平，先前证明与牙周炎的严重程度相关。牙龈微血管的变化将通过组织学切片的形态计量学分析来测量。我们将以三种不同的方式测量Pas和PAIs：基因型、细胞反应水平和体内组织水平。我们的假设表明，POA/PAI参数与牙周炎和糖尿病病理的测量结果相似，但与健康对照参与者的水平显著不同。通过基因型、细胞反应水平和体内组织水平这三种不同的方式，探讨将PAs和PAIs变化联系起来的病理生理机制。我们的假设表明，PA/PAI参数将与对照参与者相似。为了研究将PAs和PAIs变化与微血管病变发展联系起来的病理生理机制，我们将使用体外内皮细胞微血管检测系统、基质金属蛋白酶的表达和激活、基质蛋白（如IV型胶原和层粘连蛋白）的积累。预期的结果可能集中于针对牙周病和糖尿病相关病理的治疗干预，针对Pas和PAIs，并可能允许对基因典型确定的高危患者群体进行早期干预。