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PLASMINOGEN ACTIVATORS IN PERIODONTITIS AND DIABETES

牙周炎和糖尿病中的纤溶酶原激活剂

基本信息

批准号：
7123269
负责人：
ARTHUR A DECARLO
金额：
$ 2.68万
依托单位：
AGENTA BIOTECHNOLOGIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-09-30 至 2007-08-31
项目状态：
已结题

项目摘要

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为常见且更为严重。牙周炎和糖尿病患者都存在与微脉管系统相关的细胞外基质变化。我们认为，微脉管系统的变化是成人牙周炎和糖尿病组织病理学发展的常见基本过程，我们将此作为糖尿病患者牙周炎发病率和严重程度增加的解释。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 (PAI) 在血管生成和血管病以及细胞外重塑和纤维蛋白溶解中具有关键作用，因此我们建议证明 Pas 和 PAI 与牙周炎和糖尿病严重程度之间的显着相关性，并证明糖尿病患者牙周炎的恶化是 Pas 和 PAI 的函数。糖尿病相关的病理学将通过糖尿病视网膜病变的水平来测量，先前已证明与牙周炎的严重程度相关。牙龈微血管变化将通过组织切片的形态测量分析来测量。我们将以三种不同的方式测量 Pas 和 PAI：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学的测量结果类似，但与健康对照参与者的水平显着不同。解决以三种不同方式将 PA 和 PAI 变化联系起来的病理生理学机制：基因型、细胞反应水平和体内组织水平。我们的假设表明 PA/PAI 参数将与对照参与者类似地相关。为了解决将 PA 和 PAI 的变化与微血管病的发展联系起来的病理生理学机制，我们将使用体外内皮细胞微血管测定系统、基质金属蛋白酶的表达和激活以及基质蛋白（如 IV 型胶原和层粘连蛋白）的积累。预期结果可能将针对与牙周病和糖尿病相关的病理学的治疗干预的目标集中于 Pas 和 PAI，并可能允许对基因型确定处于危险中的患者群体进行早期干预。