Imaging the Vascular Consequences of Lipid Deposition

脂质沉积的血管后果成像

• 批准号: 7140908
• 负责人: JAMES Athur HAMILTON
• 金额: $ 65.18万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140908
• 关键词: atherosclerosis; atherosclerotic plaque; bariatric surgery; bioimaging /biomedical imaging; cardiovascular disorder diagnosis; cardiovascular disorder risk; cardiovascular imaging /visualization; early diagnosis; hormone metabolism; human subject; lipid metabolism; magnetic resonance imaging; metabolic syndrome; noninvasive diagnosis; obesity; pathologic process; patient oriented research; triglycerides; atherosclerosis; atherosclerotic plaque; bariatric surgery; bioimaging /biomedical imaging; cardiovascular disorder diagnosis; cardiovascular disorder risk; cardiovascular imaging /visualization; early diagnosis; hormone metabolism; human subject; lipid metabolism; magnetic resonance imaging; metabolic syndrome; noninvasive diagnosis; obesity; pathologic process; patient oriented research; triglycerides

Patients with metabolic syndrome, who are invariably obese, exhibit a cluster of risk factors for cardiovascular disease including diabetes mellitus, hypertension, and abnormalities in cholesterol metabolism. The major morbidity in such patients is myocardial infarction and stroke caused by accelerated atherosclerosis. The complex pathophysiological disturbances that promote atherogenesis also include chronic inflammation, adipocyte endocrine dysfunction, and abnormalities in vascular compliance. The development of insulin resistance is a critical underlying feature of metabolic syndrome, which results in abnormal levels of insulin and other hormones. We hypothesize that in addition to the enhanced deposition of lipid in large, well-characterized subcutaneous and visceral fat stores, another unifying feature of metabolic syndrome is innapropriate deposition of lipid in smaller depots. These inappropriate stores include hepatocellular triglyceride, perivascular and pericardial triglyceride, and atherosclerotic cholesterol, which may serve as localized markers of disease. We further hypothesize that decection of these lipid stores noninvasively in a site-specific manner will provide new insights into mechanisms by which they exert systemic effects and illuminate specific risk factors for determining adverse outcomes. Magnetic resonance imaging (MRI) is a non-invasive tool that can detect the pathological lipid deposition and identify early atherosclerotic vascular changes. We will use MR-based techniques to identify site-specific abnormalities in obese patients with metabolic syndrome but without known atherosclerosis who are undergoing medically supervised weight loss and/or gastric bypass (bariatric) surgery. We will apply MRI to identify changes in vascular stiffness and correlate these changes to the concentration of lipid in the vessel (atherosclerotic plaque) and surrounding the blood vessel (triglyceride). We will quantify triglyceride stores in the liver and surrounding the heart and blood vessels (perivascular/pericardial fat), and associate these findings with hormone levels and the presence of early atherosclerotic disease. We will monitor regression of these parameters in patients with metabolic sydnrome following successful weight loss. In patients with metabolic syndrome but advanced atherosclerosis who are undergoing carotid endarterectomy, we will use molecular MR techniques to determine evidence of inflammation and plaque vulnerability and perform in vivo and ex vivo studies to quantify lipid. This work will elucidate the complex interplay between risk factors and clinical phenotype, through the demonstration of which lipid deposits are most detrimental to future health. An important outcome our work will be a non-invasive MR-based protocol that will further stratify cardiovascular risk in this increasingly prevalent cohort of patients, and provide a means to evaluate the efficacy of specific therapies.

代谢综合征的患者总是肥胖，表现出一系列的风险因素 心血管疾病，包括糖尿病，高血压和胆固醇异常 代谢。此类患者的主要发病率是心肌梗死和中风。 动脉粥样硬化。促进动脉息护物的复杂病理生理障碍还包括 慢性炎症，脂肪细胞内分泌功能障碍和血管顺应性异常。这 胰岛素抵抗的发展是代谢综合征的关键潜在特征，这导致 胰岛素和其他激素的异常水平。我们假设除了增强的沉积外 大型，特征良好的皮下和内脏脂肪储存的脂质，另一个统一特征 代谢综合征是较小仓库中脂质的无限沉积。这些不适当的商店包括 肝细胞甘油三酸酯，周围和心包甘油三酸酯和动脉粥样硬化胆固醇 可以用作疾病的局部标记。我们进一步假设这些脂质储存的解释是无创的 以特定于地点的方式将提供有关其系统性机制的新见解 效果并照亮确定不良结果的特定风险因素。磁共振成像 （MRI）是一种非侵入性工具，可以检测病理脂质沉积并鉴定早期动脉粥样硬化 血管变化。我们将使用基于M的基于MR的技术来识别肥胖患者的现场特异性异常 患有代谢综合征，但没有已知的动脉粥样硬化，他们正在接受医学监督体重 损失和/或胃旁路（减肥）手术。我们将应用MRI来确定血管刚度的变化和 将这些变化与血管中脂质的浓度相关联（动脉粥样硬化斑块）和周围 血管（甘油三酸酯）。我们将量化肝脏中的甘油三酸酯存储，并围绕心脏和周围 血管（血管周围/心包脂肪），并将这些发现与激素水平相关联 早期动脉粥样硬化疾病的存在。我们将监视这些参数的回归。 成功减肥后代谢sydnrome。在代谢综合征的患者中，但先进 正在进行颈动脉内膜切除术的动脉粥样硬化，我们将使用分子MR技术来 确定炎症和牙菌斑脆弱性的证据，并在体内和体内进行研究 量化脂质。这项工作将阐明风险因素和临床表型之间的复杂相互作用， 通过演示，脂质沉积物最大程度不利于未来的健康。一个重要的 结果我们的工作将是一项非侵入性MR的协议，将进一步分类心血管风险 越来越普遍的患者队列，并提供了一种评估特定疗法功效的方法。