Atherosclerosis, Plaque and CVD in Communities

社区中的动脉粥样硬化、斑块和心血管疾病

• 批准号: 6718193
• 负责人: ERIC A. BOERWINKLE
• 金额: $ 436.87万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6718193
• 关键词: arteriosclerosis; atherosclerotic plaque; bioimaging /biomedical imaging; blood chemistry; cardiovascular disorder risk; carotid artery; clinical research; cooperative study; coronary disorder; disease /disorder etiology; flow cytometry; gene environment interaction; genotype; heart imaging /visualization /scanning; high throughput technology; human genetic material tag; human subject; longitudinal human study; magnetic resonance imaging; membrane structure; pathologic process; patient oriented research; proteomics; stroke; urinalysis; vascular endothelium

DESCRIPTION (provided by applicant): Experimental evidence is emerging implicating cellular and inflammatory processes in the development and characteristics of atherosclerotic plaque and the clinical course of cardiovascular disease. We propose to examine an informative subset of the bi-ethnic Atherosclerosis Risk in Communities (ARIC) cohort to identify cellular, metabolic and genomic correlates of atherosclerotic plaque characteristics and of early changes in the vascular wall. The longitudinal follow-up and stored DNA in ARIC will allow us to test the ability of the genomic correlates of plaque characteristics to predict incident coronary heart disease and stroke. One thousand two hundred individuals with high (>85th percentile) carotid artery wall thickness documented by B-mode ultrasound and 800 individuals sampled from the remainder of the carotid artery wall thickness distribution (<85th percentile) will receive a contrast-enhanced carotid MRI examination. Standardized MRI measures will include carotid artery wall thickness, T2 signal intensity changes and percent contrast enhancement indicative of endothelial dysfunction, and for those with plaque, fibrous cap thickness, lipid core volume, and calcification. Novel cellular, metabolic and genomic measures will be collected and will be related to MRI-measurable plaque characteristics. In particular, flow cytometry will be used to measure monocyte and platelet presentation of cytokines, growth factors and adhesion molecules, and cell-cell aggregation. High throughput genotyping methods will be used to measure 5 to 7 polymorphic sites in each of 150 positional, expressional and biologic candidate genes, permitting multilocus and haplotype genomic analyses. The depth and breadth of existing risk factor and lifestyle data, extensive follow-up since 1986-89, and accumulation of clinical outcomes, including coronary heart disease, stroke and arteriolosclerosis, contribute additional strengths to the laboratory and MRI investigations. Inferences will be made both cross-sectionally and longitudinally, with a special emphasis on genotype x environment interaction. The ARIC cohort is in an ideal age range for the proposed research because of the frequent and documented occurrence of plaque and the spectrum of clinically relevant stages from plaque initiation to mature fibrosis, calcification and even erosion and near-rupture. The significance of the proposed research is its potential to identify correlates of, and therefore potential mechanisms affecting, carotid artery endothelium and plaque characteristics, which in turn will lead to a better understanding of the etiology of the vulnerable plaque and the conversion of the stable to the vulnerable plaque.

描述（由申请人提供）：正在出现的实验证据表明动脉粥样硬化斑块的发展和特征以及心血管疾病的临床过程中涉及细胞和炎症过程。我们建议检查双种族动脉粥样硬化社区风险 (ARIC) 队列的一个信息子集，以确定动脉粥样硬化斑块特征和血管壁早期变化的细胞、代谢和基因组相关性。 ARIC 中的纵向随访和存储 DNA 将使我们能够测试斑块特征的基因组相关性预测冠心病和中风事件的能力。 B 型超声记录的 1200 名颈动脉壁厚较高（>85%）的个体和从其余颈动脉壁厚度分布（<85%）中取样的 800 名个体将接受对比增强颈动脉 MRI 检查。标准化 MRI 测量将包括颈动脉壁厚度、T2 信号强度变化和指示内皮功能障碍的对比增强百分比，以及有斑块、纤维帽厚度、脂质核心体积和钙化的情况。新的细胞、代谢和基因组测量将被收集，并将与 MRI 可测量的斑块特征相关。特别是，流式细胞术将用于测量单核细胞和血小板的细胞因子、生长因子和粘附分子的呈现以及细胞-细胞聚集。高通量基因分型方法将用于测量 150 个位置、表达和生物学候选基因中每个基因的 5 至 7 个多态性位点，从而允许进行多位点和单倍型基因组分析。现有危险因素和生活方式数据的深度和广度、自 1986-89 年以来的广泛随访以及包括冠心病、中风和动脉硬化在内的临床结果的积累，为实验室和 MRI 研究提供了额外的优势。将进行横向和纵向的推论，特别强调基因型与环境的相互作用。 ARIC 队列处于拟议研究的理想年龄范围，因为斑块的频繁发生和记录在案，以及从斑块起始到成熟纤维化、钙化甚至侵蚀和接近破裂的临床相关阶段的范围。这项研究的意义在于它有可能确定颈动脉内皮和斑块特征的相关性，从而确定影响颈动脉内皮和斑块特征的潜在机制，这反过来将有助于更好地了解易损斑块的病因以及稳定斑块的转变。易损斑块。