Inflammation and Vascular Dysfunction in Obesity

肥胖引起的炎症和血管功能障碍

• 批准号: 7762822
• 负责人: NOYAN GOKCE
• 金额: $ 46.79万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-20 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7762822
• 关键词: Adipocytes; Adipose tissue; Angiotensinogen; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Aorta; Area; Atherosclerosis; Bariatrics; Biology; Biometry; Biopsy; Biopsy Specimen; Blinded; Blood Vessels; Boston; Bypass; Cardiovascular Diseases; Cardiovascular system; Chronic; Clinical; Collection; Country; Disease; Disease Progression; Endocrinology; Enrollment; Epidemic; Event; Exhibits; Fatty acid glycerol esters; Functional disorder; Future; Gene Expression; Goals; Healthcare; Histologic; Histology; Homeostasis; Human; Immune; Immunohistochemistry; Individual; Infiltration; Inflammation; Inflammatory; Injury; Intervention; Investigation; Laboratories; Life; Link; Lipids; Lymphocyte; Measures; Mediating; Medical; Medical center; Metabolic; Metabolism; Obesity; Obesity associated cardiovascular disease; Operative Surgical Procedures; Overweight; Pathologist; Patients; Pharmaceutical Preparations; Phenotype; Physicians; Physiologic pulse; Population; Positioning Attribute; Production; Public Health; Public Health Schools; Randomized; Research Design; Research Personnel; Research Priority; Role; Sampling; Serum; Site; Source; Staging; Stimulus; Subgroup; Sulfasalazine; Surgeon; Systemic disease; Tissues; Toll-like receptors; Ultrasonography; Universities; Vascular Diseases; Visceral; Weight; adipokines; adiponectin; base; brachial artery; cardiovascular risk factor; care burden; experience; immune activation; improved; insulin sensitivity; intercellular cell adhesion molecule; macrophage; multidisciplinary; novel; novel strategies; nutrition; placebo controlled study; programs; response; social; subcutaneous; translational study; treatment strategy; vascular inflammation

DESCRIPTION (provided by applicant): Obesity has arguably emerged as the most serious public health problem in this country with nearly 65% of the US population currently classified as overweight or obese. The growing epidemic imposes a devastating health care burden on the nation, and there are no signs of slowing. Unprecedented numbers of individuals are exposed to increased cardiovascular risk. Inflammatory mechanisms are critical to all stages of atherosclerosis and cardiovascular disease events. The goal of the present proposal is to characterize the role of inflammation in adipose stores as a coordinator of metabolic and vascular dysfunction in obese individuals. The project is consistent with the long-term goal of the applicant to investigate mechanisms of cardiovascular disease in obesity. In addition to serving as the primary site for energy stores, fat depots are increasingly recognized as an important hotbed of metabolic and inflammatory activity, and significant synthetic source of proatherogenic and proinflammatory adipokines that orchestrate mechanisms of vascular dysfunction, injury, and cardiovascular disease progression in obesity. The extent to which a maladaptive state of inflammation in adipose tissue and adipocyte dysfunction relates to individual vascular phenotype across a wide range of obese individuals, and the effects of targeted pharmacological intervention on these parameters are critically lacking. This project proposes in specific aim 1: to relate histological inflammatory activity in human fat biopsy specimens to impaired vascular phenotype in obesity using non-invasive measures of vascular endothelial function, in specific aim 2: to determine whether inflammatory activity in human adipose tissue relates to adipocyte expression of proatherogenic adipokines quantified by rt-PCR, and in specific aim 3: to determine whether treatment with the anti-inflammatory drug sulfasalazine improves vascular dysfunction in obese patients and whether these changes relate to the level of inflammation in adipose tissue. This project proposes a highly novel approach of investigation and takes advantage of a unique multidisciplinary partnership examining mechanisms of obesity-related vascular disease in a growing area of major public health concern. These proposed studies are highly likely to yield important novel information with regard to mechanisms of vascular disease in obesity and bring us closer to identifying optimal treatment strategies firmly relevant to the future management of overweight and obese patients.

描述（由申请人提供）：肥胖可以说已成为美国最严重的公共卫生问题，目前近 65% 的美国人口属于超重或肥胖。日益严重的流行病给国家带来了毁灭性的医疗负担，而且没有任何放缓的迹象。心血管风险增加的人数空前多。炎症机制对于动脉粥样硬化和心血管疾病事件的所有阶段都至关重要。本提案的目标是描述脂肪储存中炎症作为肥胖个体代谢和血管功能障碍的协调者的作用。该项目与申请人研究肥胖引起的心血管疾病机制的长期目标一致。除了作为能量储存的主要场所外，脂肪库越来越被认为是代谢和炎症活动的重要温床，也是促动脉粥样硬化和促炎症脂肪因子的重要合成来源，这些脂肪因子协调血管功能障碍、损伤和心血管疾病进展的机制。肥胖。脂肪组织中的炎症适应不良状态和脂肪细胞功能障碍与广泛肥胖个体的个体血管表型相关，并且非常缺乏针对性的药物干预对这些参数的影响。该项目提出的具体目标 1：利用血管内皮功能的非侵入性测量，将人体脂肪活检标本中的组织学炎症活动与肥胖症受损的血管表型联系起来，具体目标 2：确定人体脂肪组织中的炎症活动是否与肥胖相关通过 rt-PCR 量化促动脉粥样硬化脂肪因子的脂肪细胞表达，具体目标 3：确定抗炎药物柳氮磺胺吡啶治疗是否可以改善血管肥胖患者的功能障碍以及这些变化是否与脂肪组织的炎症水平有关。该项目提出了一种高度新颖的研究方法，并利用独特的多学科合作伙伴关系，在日益受到关注的主要公共卫生领域中检查与肥胖相关的血管疾病的机制。这些拟议的研究很可能产生有关肥胖症血管疾病机制的重要新信息，并使我们更接近于确定与超重和肥胖患者的未来管理密切相关的最佳治疗策略。