Vascular Consequences of Insulin Resistance and Obesity
胰岛素抵抗和肥胖对血管的影响
基本信息
- 批准号:7621045
- 负责人:
- 金额:$ 228.82万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant):
Patients with obesity-related phenomena such as insulin resistance, the metabolic syndrome, and Type 2 diabetes mellitus, have a markedly increased risk for atherothrombosis. Investigators now recognize these conditions as representing a major threat to public health and that our current understanding and management strategies of these disorders are inadequate. Studies suggest that excess caloric intake and physical inactivity lead to a neuro-humoral imbalance that promotes obesity and insulin resistance in association with systemic inflammation and dyslipidemia. In the vascular wall, systemic factors and local insulin resistance combine to alter cellular energetics and mitochondrial function, activate innate immunity, and impair the bioavailability of endothelium-derived nitric oxide. We propose to establish a Specialized Center of Clinically-Oriented Research (SCCOR) at Boston University School of Medicine that will take a multi-disciplinary approach to define mechanisms of vascular injury in this setting. We will test the overall hypothesis that obesity and insulin resistance induce inflammation and ectopic lipid deposition in vasculature that impairs vascular function and promotes atherothrombosis. Project 1 (Dr. Vita) will test the hypothesis that inter-related effects of reduced activity of AMP-dependent protein kinase, increased production of mitochondrial-derived reactive oxygen species, and activation of innate immunity contribute to vascular dysfunction in human subjects with early insulin resistance. Project 2 (Dr. Ramachandran) will test the hypothesis that circulating adipokines and neuroendocrine and gut-derived hormones impair vascular function and will prospectively predict risk for developing obesity, hypertension, dyslipidemia, and the metabolic syndrome in the Framingham Heart Study. Project 3 (Dr. Gokce) will test the hypothesis that adipose tissue serves as a primary source of inflammatory cytokines that impair vascular function in obese patients and will examine the impact of specific weight loss strategies on vascular function and inflammation in adipose tissue. Project 4 (Dr. Freedman) will test the hypothesis that innate immunity contributes to atherothrombosis and the acute response to vascular injury by examining toll-like receptor (TLR)-mediated signaling mechanisms in leukocytes and platelets from human subjects and mouse models of obesity. Project 5 (Dr. Hamilton) will use novel magnetic resonance imaging and spectroscopy techniques to test the hypothesis that ectopic lipid deposition is a marker of vascular dysfunction and accelerated atherosclerosis in obesity and the metabolic syndrome. This project takes advantage of the unique expertise of the investigators and research resources at the Boston University Medical Campus, including strong statistical support, outstanding programs of research in basic vascular biology, novel imaging resources, clinical programs for the management of obesity, and the Framingham Heart Study. This work will improve our understanding of vascular injury in insulin resistance and obesity and may identify new approaches for patient management.
描述(由申请人提供):
患有胰岛素抵抗、代谢综合征和 2 型糖尿病等肥胖相关现象的患者,动脉粥样硬化血栓形成的风险显着增加。研究人员现在认识到这些疾病对公共健康构成了重大威胁,并且我们目前对这些疾病的理解和管理策略还不够。研究表明,热量摄入过多和缺乏身体活动会导致神经体液失衡,从而促进肥胖和胰岛素抵抗,并与全身炎症和血脂异常相关。在血管壁中,全身因素和局部胰岛素抵抗结合起来改变细胞能量学和线粒体功能,激活先天免疫,并损害内皮源性一氧化氮的生物利用度。我们建议在波士顿大学医学院建立一个临床导向研究专业中心(SCCOR),该中心将采用多学科方法来定义这种情况下的血管损伤机制。我们将检验总体假设,即肥胖和胰岛素抵抗会引起脉管系统中的炎症和异位脂质沉积,从而损害血管功能并促进动脉粥样硬化血栓形成。项目 1(Vita 博士)将测试以下假设:AMP 依赖性蛋白激酶活性降低、线粒体衍生活性氧生成增加以及先天免疫激活等相互关联的影响会导致患有早期血管疾病的人类受试者的血管功能障碍。胰岛素抵抗。项目 2(Ramachandran 博士)将测试循环脂肪因子、神经内分泌和肠道源性激素损害血管功能的假设,并将前瞻性预测弗雷明汉心脏研究中发生肥胖、高血压、血脂异常和代谢综合征的风险。项目 3(Gokce 博士)将检验脂肪组织是损害肥胖患者血管功能的炎症细胞因子主要来源的假设,并将研究特定减肥策略对脂肪组织血管功能和炎症的影响。项目 4(Freedman 博士)将通过检查人类受试者和肥胖小鼠模型的白细胞和血小板中 Toll 样受体 (TLR) 介导的信号传导机制,检验先天免疫导致动脉粥样硬化血栓形成和对血管损伤的急性反应的假设。项目 5(汉密尔顿博士)将使用新型磁共振成像和光谱技术来检验以下假设:异位脂质沉积是肥胖和代谢综合征中血管功能障碍和加速动脉粥样硬化的标志。该项目利用了波士顿大学医学校区研究人员的独特专业知识和研究资源,包括强大的统计支持、基础血管生物学的杰出研究项目、新颖的成像资源、肥胖管理的临床项目以及弗雷明汉心脏研究。这项工作将提高我们对胰岛素抵抗和肥胖引起的血管损伤的理解,并可能确定患者管理的新方法。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Joseph A. Vita其他文献
Nitric Oxide and the Cardiovascular System
一氧化氮与心血管系统
- DOI:
10.1007/978-1-59259-002-5 - 发表时间:
2024-09-14 - 期刊:
- 影响因子:4.8
- 作者:
J. Loscalzo;Joseph A. Vita - 通讯作者:
Joseph A. Vita
Epicardial coronary artery responses to acetylcholine are impaired in hypertensive patients.
高血压患者心外膜冠状动脉对乙酰胆碱的反应受损。
- DOI:
10.1161/01.res.71.4.776 - 发表时间:
1992-10-01 - 期刊:
- 影响因子:20.1
- 作者:
C. Treasure;S. Manoukian;J. Klein;Joseph A. Vita;E. G. Nabel;George H. Renwick;A. Selwyn;R. Ale;er;er - 通讯作者:
er
Usefulness and tolerability of hirulog, a direct thrombin-inhibitor, in unstable angina pectoris.
水蛭素(一种直接凝血酶抑制剂)在不稳定型心绞痛中的用途和耐受性。
- DOI:
10.1016/0002-9149(93)90179-g - 发表时间:
1993-12-15 - 期刊:
- 影响因子:0
- 作者:
Gaurav Sharma;Gaurav Sharma;Gaurav Sharma;D. Lapsley;D. Lapsley;D. Lapsley;Joseph A. Vita;Joseph A. Vita;Joseph A. Vita;Satish C. Sharma;Satish C. Sharma;Satish C. Sharma;Elizabeth Coccio;Elizabeth Coccio;Elizabeth Coccio;Burt Adelman;Burt Adelman;Burt Adelman;Joseph Loscalzo;Joseph Loscalzo;Joseph Loscalzo - 通讯作者:
Joseph Loscalzo
Enhanced nitric oxide-mediated vascular relaxation in radial artery compared with internal mammary artery or saphenous vein.
与乳内动脉或隐静脉相比,桡动脉中一氧化氮介导的血管舒张增强。
- DOI:
10.1161/01.cir.100.suppl_2.ii-322 - 发表时间:
1999-11-09 - 期刊:
- 影响因子:37.8
- 作者:
O. Shapira;Aiming Xu;Gabriel S. Aldea;Joseph A. Vita;R. Shemin;John F. Keaney - 通讯作者:
John F. Keaney
Endothelial function and clinical outcome
内皮功能和临床结果
- DOI:
10.1136/hrt.2005.061333 - 发表时间:
2005-09-14 - 期刊:
- 影响因子:5.7
- 作者:
Joseph A. Vita - 通讯作者:
Joseph A. Vita
Joseph A. Vita的其他文献
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{{ truncateString('Joseph A. Vita', 18)}}的其他基金
Mitochondrial Dynamics and UCP2 - Endothelial Dysfunction in Human Obesity
线粒体动力学和 UCP2 - 人类肥胖中的内皮功能障碍
- 批准号:
8583774 - 财政年份:2013
- 资助金额:
$ 228.82万 - 项目类别:
MITOCHONDRIAL DYSFUNCTION IN THE DIABETIC ENDOTHELIUM
糖尿病内皮线粒体功能障碍
- 批准号:
8109656 - 财政年份:2011
- 资助金额:
$ 228.82万 - 项目类别:
Boston University Medical Center Leadership Program in Vascular Medicine
波士顿大学医学中心血管医学领导力项目
- 批准号:
7351857 - 财政年份:2007
- 资助金额:
$ 228.82万 - 项目类别:
Boston University Medical Center Leadership Program in Vascular Medicine
波士顿大学医学中心血管医学领导力项目
- 批准号:
7767681 - 财政年份:2007
- 资助金额:
$ 228.82万 - 项目类别:
Boston University Medical Center Leadership Program in Vascular Medicine
波士顿大学医学中心血管医学领导力项目
- 批准号:
7066895 - 财政年份:2007
- 资助金额:
$ 228.82万 - 项目类别:
Boston University Medical Center Leadership Program in Vascular Medicine
波士顿大学医学中心血管医学领导力项目
- 批准号:
7566010 - 财政年份:2007
- 资助金额:
$ 228.82万 - 项目类别:
Vascular Consequences of Insulin Resistance and Obesity
胰岛素抵抗和肥胖对血管的影响
- 批准号:
7418248 - 财政年份:2006
- 资助金额:
$ 228.82万 - 项目类别:
Vascular Consequences of Insulin Resistance and Obesity
胰岛素抵抗和肥胖对血管的影响
- 批准号:
7227535 - 财政年份:2006
- 资助金额:
$ 228.82万 - 项目类别:
Mechanisms of Vascular Dysfunction in Acute Insulin Resistance
急性胰岛素抵抗中血管功能障碍的机制
- 批准号:
7140900 - 财政年份:2006
- 资助金额:
$ 228.82万 - 项目类别:
Determinants of Shear Stress-Mediated Arterial Remodeling
剪应力介导的动脉重塑的决定因素
- 批准号:
7452358 - 财政年份:2006
- 资助金额:
$ 228.82万 - 项目类别:
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