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: 7052858
• 负责人: Valentin Fuster
• 金额: $ 13.97万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7052858
• 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中包含活性组织因子（TF），这可能导致血栓形成增强。动脉粥样硬化疾病的危险因素，例如高胆固醇血症，吸烟和2型糖尿病，可能部分地充当了增强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（AC）中，没有通常的富含脂质的斑块的通常破坏，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上述危险因素（例如上述危险因素）触发的血栓形成性TF的增加。我们将检验以下假设：在高胆固醇血症，2型糖尿病和吸烟者中，在患有高胆固醇血症的个体中发现了增强的血栓形成和循环组织因子（TF）活性（AIM 1A）；通过修改风险因素修饰方法，将获得降低的血栓形成性和循环TF活性的归一化（AIM 1B）。在两名患有动脉粥样硬化疾病和高胆固醇血症的患者中，循环TF活性的变化将与过度胆固醇血症的改变以及通过斑块回归/稳定性/稳定性稳定/稳定性的进展速率（通过非侵入性磁共振成像（MIRI）的caroties antries Arta和carotic anta Inorta Inorta（MIR）（MIR）（MIR）（MIR）（MIR）（MIR）（MIR）相关。 2A）和通过另一个队列中的侵入性冠状动脉内超声（IVU）（AIM 2B）。最后，在正在进行的妇女健康研究中，将接触TF活动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型糖尿病或吸烟糖尿病的存在之间的关系（AIM 3B）。血小板 - 血浆中的白细胞聚集体以及血浆中血浆中血浆的活化也将作为各种目的的一部分测量。