Blood tissue factor activity, risk factors and CAD

血液组织因子活性、危险因素和 CAD

• 批准号: 6446685
• 负责人: VALENTIN FUSTER
• 金额: $ 12.64万
• 依托单位: MOUNT SINAI SCHOOL OF MEDICINE OF CUNY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-03-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6446685
• 关键词: acute phase protein; angiocardioultrasonography; angiography; atherosclerotic plaque; blood chemistry; blood coagulation; disease /disorder proneness /risk; human subject; hypercholesterolemia; magnetic resonance imaging; molecular pathology; noninsulin dependent diabetes mellitus; patient oriented research; platelet activation; smoking; thromboembolism; thromboplastin; thrombosis; tobacco abuse

DESCRIPTION (Applicant's Abstract) There is evolving evidence that circulating blood contains active tissue factor (TF) and that this may lead to enhanced blood thrombogenicity. Risk factors for atherosclerotic disease, such as hypercholesterolemia, cigarette smoking, and diabetes type 2 may in part act as triggers of enhanced blood thrombogenicity. In about a third of acute coronary syndromes (ACS) there is not the usual disruption of a small lipid-rich plaque but just a superficial erosion of a stenotic and fibrotic plaque (Fig 1). Thus, complicated thrombi in such cases may well be the result of an increased blood thrombogenicity- TF dependent, triggered by systemic risk factors such as those mentioned above. We will test the hypothesis that enhanced blood thrombogenicity and circulating tissue factor (TF) activity will be found in individuals with hypercholesterolemia, with diabetes type 2 and in cigarette smokers (AIM 1a); decreased thrombogenicity and normalization of circulating TF activity will be obtained with risk factor modifying approaches (AIM 1b). In two cohorts of patients with atherosclerotic disease and hypercholesterolemia, changes in circulating TF activity will be correlated with modification of hypercholesterolemia and with primary efficacy as measured by the rate of plaque regression/stabilization/progression by noninvasive magnetic resonance imaging (MRI) of the carotid arteries, thoracic aorta and coronary arteries in one cohort (AIM 2a) and by invasive coronary intravascular ultrasound (IVUS)in the other cohort (AIM 2b). Finally, in the ongoing women's Health Study, the relationship between circulating TF activity and cardiovascular events will be approached (AIM 3a), as well as the relationship between these two parameters and the presence of hypercholesterolemia, diabetes type 2 or cigarette smoking (AIM 3b). Platelet - leukocyte aggregates and activation in blood and C-reactive protein (CRP) in plasma will also be measured as part of the various aims.

描述（申请人的摘要）有不断发展的证据表明循环血液含有活性组织因子（TF），并且这可能导致增强的血液促凝性。动脉粥样硬化疾病的危险因素，如高胆固醇血症、吸烟和2型糖尿病可能部分地作为增强的血液血栓形成的触发因素。在大约三分之一的急性冠状动脉综合征（ACS）中，没有通常的富含脂质的小斑块破裂，而只是狭窄和纤维化斑块的表面侵蚀（图1）。因此，在这种情况下，复杂的血栓很可能是由于增加的血液促凝性- TF依赖性，由全身性风险因素，如上述那些触发。我们将检验以下假设：高胆固醇血症、2型糖尿病和吸烟者（AIM 1a）的血液促凝性和循环组织因子（TF）活性增强;风险因子修饰方法（AIM 1b）可降低促凝性和使循环TF活性正常化。在患有动脉粥样硬化性疾病和高胆固醇血症的两个患者队列中，循环TF活性的变化将与高胆固醇血症的改善和主要疗效相关，主要疗效通过颈动脉的无创磁共振成像（MRI）的斑块消退/稳定/进展速率测量，在一个队列中（AIM 2a）通过胸主动脉和冠状动脉，在另一个队列中（AIM 2b）通过侵入性冠状动脉血管内超声（IVUS）。最后，在正在进行的女性健康研究中，将探讨循环TF活性与心血管事件之间的关系（AIM 3a），以及这两个参数与高胆固醇血症、2型糖尿病或吸烟之间的关系（AIM 3b）。作为各种目标的一部分，还将测量血液中的血小板-白细胞聚集体和活化以及血浆中的C反应蛋白（CRP）。