Imaging the Vascular Consequences of Lipid Deposition

患有代谢综合征的患者总是肥胖的，他们表现出一系列危险因素， 心血管疾病，包括糖尿病、高血压和胆固醇异常 新陈代谢.这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粥样硬化形成的复杂病理生理学紊乱还包括 慢性炎症、脂肪细胞内分泌功能障碍和血管顺应性异常。的 胰岛素抵抗的发展是代谢综合征的一个关键的潜在特征，其导致 胰岛素和其他激素水平异常。我们推测除了沉积物的增加 脂肪在大的，特征良好的皮下和内脏脂肪储存，另一个统一的特点， 代谢综合征是脂质在较小的贮库中的不适当沉积。这些不合适的商店包括 肝细胞甘油三酯、血管周围和心包甘油三酯和动脉粥样硬化胆固醇， 可以作为疾病的局部标记。我们进一步假设，这些脂质储存的非侵入性检测 将提供新的见解的机制，他们发挥系统性 影响并阐明确定不良结局的特定风险因素。磁共振成像 (MRI)是一种非侵入性的工具，可以检测病理性脂质沉积，并识别早期动脉粥样硬化 血管变化我们将使用基于磁共振的技术来确定肥胖患者的特定部位异常 患有代谢综合征，但没有已知的动脉粥样硬化，正在接受医学监督的体重 减肥和/或胃旁路（减肥）手术。我们将应用MRI来识别血管僵硬度的变化， 将这些变化与血管（动脉粥样硬化斑块）和周围的脂质浓度相关联， 血管（甘油三酯）。我们将量化肝脏和心脏周围的甘油三酯储存， 血管（血管周围/心包脂肪），并将这些发现与激素水平和 存在早期动脉粥样硬化疾病。我们将监测这些参数的回归患者， 成功减肥后的代谢综合征。在患有代谢综合征但晚期 对于正在接受颈动脉内膜切除术的动脉粥样硬化患者，我们将使用分子MR技术， 确定炎症和斑块易损性的证据，并进行体内和体外研究， 量化脂质。这项工作将阐明危险因素和临床表型之间复杂的相互作用， 通过证明哪些脂质沉积物对未来健康最有害。一个重要 结果我们的工作将是一个非侵入性的MR为基础的协议，将进一步分层心血管疾病的风险， 越来越普遍的患者队列，并提供一种手段来评估特定疗法的疗效。

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.