EFFECTS OF CHRONIC GREEN TEA FLAVONOID SUPPLEMENTATION ON BIOMARKERS OF OXIDATI

长期补充绿茶类黄酮对氧化生物标志物的影响

• 批准号: 7608119
• 负责人: TIMOTHY J LYONS
• 金额: $ 0.49万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7608119
• 关键词: Adult; Amputation; Architecture; Arterial Fatty Streak; Arteries; Atherectomy; Atherosclerosis; Biochemical Markers; Biological Markers; Blood; Blood Circulation; Blood Platelets; Blood Vessels; Blood specimen; Catheterization; Chronic; Collagen; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Diabetes Mellitus; Diffuse; Disease; Distal; Excess Mortality; Female; Flavonoids; Funding; Grant; Green tea; Histologic; Hypertension; Inflammation; Inflammatory; Institution; Interleukin-6; Intermittent Claudication; Intervention; Ischemia; Laboratories; Leukocytes; Limb structure; Lipids; Lower Extremity; Measures; Medical center; Methods; Morbidity - disease rate; Nitric Oxide Synthase; Non-Insulin-Dependent Diabetes Mellitus; Oxidative Stress; Patients; Peripheral; Presbyterian Church; Preventive; Process; Prostaglandin-Endoperoxide Synthase; Research; Research Design; Research Personnel; Resources; Risk Factors; Risk Marker; Sample Size; Sampling; Serum; Smoking; Source; Supplementation; TNF gene; Therapeutic Intervention; Thrombin; Tissues; United States National Institutes of Health; Urine; Variant; cardiovascular risk factor; clinically significant; cyclooxygenase 1; cyclooxygenase 2; cysteine rich protein; diabetic; disorder risk; insight; male; non-diabetic; novel; receptor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To gather data on 'the differences in disease-related biochemical markers in adult patients with lower extremity atherosclerotic disease (LEAD) with type 2 diabetes vs non-diabetics' to estimate variations in proposed measures and sample sizes of the larger planned study. Specific Aims: 1. In atheromatous plaque obtained from lower extremity arteries of adult patients with type 2 diabetes vs non-diabetics, determine the differences among tissue levels and types of biochemical markers, modulators, and receptors of inflammation and oxidative stress (eg, nitric oxide synthase and cyclooxygenase), and the histologic architecture;2. In blood samples of adult patients with LEAD with type 2 diabetes vs non-diabetics, determine the differences among levels and types of biochemical markers, modulators, and receptors of inflammation and oxidative stress (eg, nitric oxide synthase and cyclooxygenase) in leukocytes and platelets, and the quantities of 'collagen and thrombin' activated (COAT) platelets;3. In the serum and urine of adult patients with LEAD with type 2 diabetes vs non-diabetics, determine the differences among levels of biochemical markers of inflammation, oxidative stress (eg, CRP, IL-6, TNF-?, CAP-37), and cardiovascular risk (eg, A1C, lipid profile, urine microalbumin).Research Design and Methods: A cross-sectional research design (N = 40; 20 type 2 diabetic and 20 nondiabetic, 10 male and 10 female in each group) will allow for the determination of the differences and the examination of the relationship among biochemical markers, modulators, and receptors of inflammation and oxidative stress, in atheromatous plaques of lower extremities, and in leukocytes and platelets obtained from blood samples, and serum inflammatory and cardiovascular risk markers, after controlling for vascular risk factors and other co morbidities in patients with LEAD with type 2 diabetes vs non-diabetics. Atheromatous plaque, blood and urine samples will be obtained from patients with LEAD, who undergo elective atherectomy in the peripheral intervention catheterization laboratory of Presbyterian Tower (OU Medical Center). Biochemical markers, modulators, and receptors of inflammation and oxidative stress will be assessed in plaques, platelets and leukocytes, and markers of inflammation and cardiovascular risk will be measured in the serum of these patients. Histologic examination of the plaque will be performed as well. Clinical Significance: Type 2 diabetes is most strongly associated with diffuse and distal (i.e., femoropopliteal and tibial) atherosclerotic processes, causing intermittent claudication (IC) or chronic critical limb ischemia (CCLI); whereas, other LEAD risk factors (e.g., smoking and hypertension) are associated with more proximal disease in the aorto-iliofemoral vessels. CCLI is a major risk factor for lower-extremity amputation and excess mortality in patients with diabetes. Identifying the diabetes-related changes of inflammation and oxidative stress in atheroma, platelets, and leukocytes, and biochemical markers of inflammation, oxidative stress and cardiovascular risk in circulation and urine independent of vascular risk factors and co morbidities will provide pertinent insight reflecting the unique contribution of the inflammation, oxidative stress, and the circulating inflammatory & cardiovascular risk markers in underlying pathophysiological processes of LEAD in diabetes vs non-diabetics. This understanding of the pathophysiologic mechanisms in diabetes will facilitate development of novel preventive and/or therapeutic interventions for atherosclerosis in diabetes.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目的：收集“下肢动脉粥样硬化性疾病（LEAD）伴2型糖尿病成人患者与非糖尿病患者疾病相关生化标志物差异”的数据，以估计拟定测量值和大型计划研究样本量的变化。具体目标：1。 在从2型糖尿病与非糖尿病成人患者下肢动脉获得的动脉粥样硬化斑块中，确定组织水平和类型的生化标志物、炎症和氧化应激的调节剂和受体（例如，一氧化氮合酶和环氧合酶）以及组织学结构之间的差异;2. 在2型糖尿病与非糖尿病的成人LEAD患者的血液样本中，确定白细胞和血小板中的炎症和氧化应激的生化标志物、调节剂和受体（例如，一氧化氮合酶和环氧合酶）的水平和类型之间的差异，以及“胶原和凝血酶”活化（COAT）血小板的数量;3. 在2型糖尿病与非糖尿病的成人LEAD患者的血清和尿液中，确定炎症、氧化应激（如CRP、IL-6、TNF-？、CAP-37）和心血管风险（如A1 C、血脂、尿微量白蛋白）。研究设计和方法：横断面研究设计（N = 40; 20名2型糖尿病患者和20名非糖尿病患者，每组10名男性和10名女性）将允许测定差异和检查生化标记物，调节剂，以及炎症和氧化应激的受体，下肢动脉粥样硬化斑块，以及从血液样本中获得的白细胞和血小板，以及血清炎症和心血管风险标志物，在控制血管风险因素和其他并发症后，在患有LEAD的2型糖尿病患者与非糖尿病患者中进行比较。 动脉粥样硬化斑块、血液和尿液样本将从在Presbyterian Tower外周介入导管实验室（ESSEC Medical Center）接受择期斑块切除术的LEAD患者中获得。将在斑块、血小板和白细胞中评估炎症和氧化应激的生化标志物、调节剂和受体，并将在这些患者的血清中测量炎症和心血管风险的标志物。还将对斑块进行组织学检查。 临床意义：2型糖尿病与弥漫性和远端（即，股腘动脉和胫骨）动脉粥样硬化过程，导致间歇性跛行（IC）或慢性严重肢体缺血（CCLI）;而其他LEAD风险因素（例如，吸烟和高血压）与髂髂股血管中更近端的疾病相关。 CCLI是糖尿病患者下肢截肢和高死亡率的主要危险因素。确定动脉粥样硬化、血小板和白细胞中炎症和氧化应激的糖尿病相关变化，以及循环和尿液中炎症、氧化应激和心血管风险的生物化学标志物，与血管风险因素和并发症无关，将提供反映炎症、氧化应激、以及糖尿病患者与非糖尿病患者LEAD潜在病理生理过程中的循环炎症和心血管风险标志物。对糖尿病病理生理机制的理解将有助于开发糖尿病动脉粥样硬化的新的预防和/或治疗干预措施。