Metabolic Syndrome, Inflammation and Vascular Remodeling

代谢综合征、炎症和血管重塑

• 批准号: 7228892
• 负责人: FRANCINE K WELTY
• 金额: $ 256.05万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7228892
• 关键词: Metabolic; Syndrome; Inflammation; Vascular; Remodeling

DESCRIPTION (provided by applicant): "Metabolic Syndrome, Inflammation, and Vascular Remodeling" is the central theme of this SCCOR. Inflammation is increasingly accepted as a major contributor to the pathogenesis of coronary heart disease (CHD) and type 2 diabetes. Insulin resistance and the metabolic syndrome appear to be at the root of the pathogenic process. In this SCCOR grant we have united important new discoveries in diverse areas of research to determine whether primary targeting of inflammation as a therapeutic goal provides a new route to treat CHD. We will target inflammation via lifestyle intervention, indirectly using PPARa agonists, and directly by inhibiting the NF-KB pathway, the master switch of inflammation. We will combine these novel series of interventions with a newly developing, state-of-the-art, minimally invasive imaging technique, multidetector computed tomographic angiography (MDCTA) that examines dynamic processes in the coronary circulation, including the development and regression of soft and hard plaques. Specific Aims include: Project by Shoelson: To determine how obesity- and Western diet-induced inflammation influences CHD in animal models. We have discovered that obesity activates a subacute inflammatory process in fat and liver via NF-KB, which leads to the production of cytokines and causes systemic insulin resistance. We have hypothesized that the obesity-driven production of these cytokines promotes CHD and will test this in relevant rodent models. In a series of three clinical projects we will use different interventions to target subacute inflammation in patients with established CHD and assess the effect of the interventions on regression of soft plaque assessed by MDCTA. Project by Welty: Since Western diet and obesity activate the NF-KB cascade, we hypothesize that weight loss achieved through dietary and exercise intervention will suppress the subacute inflammatory process to promote vascular remodeling and regression of soft plaque, and in Project by Goldfarb: We will directly target the inflammatory signaling

描述（由申请人提供）： SCCOR的中心主题是“代谢综合征，炎症和血管重塑”。炎症越来越被视为冠状动脉疾病（CHD）和2型糖尿病的发病机理的主要贡献者。胰岛素抵抗和代谢综合征似乎是致病过程的根源。在这项SCCOR赠款中，我们在不同的研究领域有了重要的新发现，以确定将炎症作为治疗目标的主要靶向是否提供了治疗CHD的新途径。我们将通过生活方式干预，间接使用PPARA激动剂来靶向炎症，直接通过抑制NF-KB途径，即炎症的主开关。我们将将这些新颖的一系列干预措施与新开发的，最先进的，微创的成像技术，多探测器计算机层析成像层学血管造影（MDCTA）相结合，该技术检查冠状动脉循环中的动态过程，包括软和硬质斑块的发展和回归。具体目的包括：Shoelson项目：确定肥胖症和西方饮食引起的炎症如何影响动物模型中的CHD。我们发现，肥胖症通过NF-KB激活脂肪和肝脏中的亚急性炎症过程，这导致细胞因子的产生并引起全身性胰岛素抵抗。我们假设这些细胞因子的肥胖驱动的产生会促进CHD，并将在相关的啮齿动物模型中对其进行测试。在一系列三个临床项目中，我们将使用不同的干预措施来靶向已建立的冠心病患者的亚急性炎症，并评估MDCTA评估的软斑块回归的影响。 Welty的项目：由于西方饮食和肥胖激活了NF-KB级联反应，我们假设通过饮食和运动干预实现的体重减轻将抑制亚急性炎症过程，以促进软质块状的血管重塑和回归，而在Goldfarb中，我们将直接靶向炎症信号传导，