Pathobiology of Macrovascular Disease in Diabetes

糖尿病大血管疾病的病理学

基本信息

批准号：
7470432
负责人：
ALAN CHAIT
金额：
$ 13.93万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
1976
资助国家：
美国
起止时间：
1976-09-01 至 2008-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7470432
关键词：
Accounting Address Advanced Glycosylation End Products Amino Acids Animal Experimentation Animal Model Animals Antioxidants Apolipoprotein E Apolipoproteins Area Arterial Fatty Streak Arteries Atherosclerosis Biochemical Biochemical Pathway Biological Markers Biological Models Biological Process Biology Blood Blood Glucose Blood Vessels Candidate Disease Gene Cardiac Cardiovascular Diseases Cardiovascular system Cause of Death Cell Line Cell Nucleus Cell model Cell physiology Cell surface Cells Cellular biology Central obesity Chemistry Cholesterol Chronic Clinical Research Clinical Trials Collaborations Collection Complex Complications of Diabetes Mellitus Control Animal Core Protein Coronary Arteriosclerosis Cost Savings Coupled Data Defect Development Diabetes Mellitus Diabetic Angiopathies Diabetic macrovascular disease Diet Discipline Disease Doctor of Philosophy Drug Delivery Systems Equipment Event Experimental Animal Model Experimental Designs Experimental Models Extracellular Matrix Fertilization Funding Future Genes Genetic Genetic Models Genetic Predisposition to Disease Glucose Glycosaminoglycans Goals Grant Growth Factor Heart Transplantation High Density Lipoprotein Cholesterol Hip region structure Human Human Resources Hyaluronan Hyperglycemia Hyperlipidemia Hypertension In Situ Hybridization In Vitro Incidence Individual Injury Insulin Insulin Resistance Insulin-Dependent Diabetes Mellitus Intra-abdominal Investigation Ions Isoprostanes Joints Kidney Kidney Diseases Knowledge Laboratories Lead Leadership Link Lipid Peroxidation Lipids Lipoproteins Localized Low Density Lipoprotein oxidation Low-Density Lipoproteins Mass Spectrum Analysis Measures Mediating Metabolic Metabolic syndrome Metals Methods Mitochondria Modeling Molecular Molecular Abnormality Molecular Profiling Morbidity - disease rate Mus Nature Non-Insulin-Dependent Diabetes Mellitus Nonesterified Fatty Acids Numbers Operative Surgical Procedures Other Genetics Oxidative Stress Parents Participant Pathogenesis Pathology Pathway interactions Patients Peptide Mapping Peptides Phagocytes Phenotype Plasma Platelet aggregation Play Polyunsaturated Fatty Acids Prevention Principal Investigator Procedures Process Production Productivity Program Evaluation Program Research Project Grants Property Protein Chemistry Protein Kinase C Proteins Proteoglycan Proteomics Public Health Publishing Range Reaction Reagent Regulation Relative (related person)Research Research Personnel Research Priority Resource Sharing Resources Risk Risk Factors Role Science Scientist Services Signal Transduction Smooth Muscle Myocytes Specimen Staging Sterols Streptozocin Stress Subgroup Syndrome Techniques Testing Therapeutic Tissue Harvesting Tissue Sample Tissues Title Transplant Recipients Two-Dimensional Gel Electrophoresis Tyrosine Uncertainty Universities Vascular Diseases Vision Vitamin E Vitamins Washington Weight Whole Organism Work abdominal fat animal tissue atherogenesis biglycan body system carbonyl compound cardiovascular disorder risk cardiovascular risk factor cell type citrate carrier cohort cytokine day design diabetes mellitus genetics diabetic follow-up glycation glycemic control human subject in vivo innovation insight interest macrophage macrovascular disease mitochondrial dysfunction monocyte mortality mouse model non-diabetic nonhuman primate novel oxidation particle prevent programs reverse cholesterol transport skills tool type I and type II diabetes type I diabetic

项目摘要

PROVIDED. The overall objective of this program project is to better understand mechanisms involved in the pathogenesis of macrovascular disease in diabetes, which is the major cause of morbidity and mortality in both type 1, and especially type 2 diabetes. Its goal is to better understand the genetic, cellular, biochemical and molecular nature of the premature atherosclerosis that characterizes the diabetic state. The program project is comprised of 4 inter-related projects and 3 cores. Project 1will study the interaction of atherogenic lipoproteins with extracellular matrix molecules that result in the retention of these lipoproteins in the vascular wall, thereby enhancing atherosclerosis. It will focus on the regulation of these matrix molecules by factors associated with the diabetic state that facilitate lipoprotein retention. Project 2 is aimed at understanding why a subgroup of intensively-treated patients with type 1 diabetes develop features of type 2 diabetes such as central obesity, insulin resistance, and the associated cardiovascular risk factors that put these individuals at increased risk of premature cardiovascular and renal disease. Project 3 will study the role of diabetes on the regulation of the newly described cellular transporter, ABCA1, which plays a critical role in reverse cholesterol transport. Defects in the ability to remove cholesterol from the artery wall can result in increased atherogenesis. Project 4 will study the biochemical pathways involved in glycation and glycoxidation reactions that play a role in damaging various vascular lipids and proteins, thereby accelerating atherosclerosis in diabetes. These projects will be supported by an administrative and 2 scientific cores: The Arterial Tissue and Applied Pathology Core will provide 3 of the projects with arterial tissue from human subjects with diabetes and from several animal models. The Protein Chemistry Core will provide sophisticated biochemical support for the in vitro and in vivo studies proposed in all the projects. The increased understanding of the pathogenesis of the premature vascular disease in diabetes that will be derived from each of the projects has important therapeutic implications for the prevention and treatment of macrovascular disease in diabetes.

假如。该计划项目的总体目标是更好地了解发病机制糖尿病中的大血管疾病，这是 1 型和 1 型糖尿病发病率和死亡率的主要原因尤其是2型糖尿病。其目标是更好地了解遗传、细胞、生化和分子糖尿病状态特征的过早动脉粥样硬化的性质。该计划项目包括 4 个相互关联的项目和 3 个核心。项目 1 将研究致动脉粥样硬化脂蛋白与细胞外基质分子导致这些脂蛋白保留在血管壁中，从而增强动脉粥样硬化。它将重点关注与相关因素对这些基质分子的调节促进脂蛋白保留的糖尿病状态。项目 2 旨在理解为什么一个子组接受强化治疗的 1 型糖尿病患者会出现 2 型糖尿病的特征，例如向心性肥胖、胰岛素抵抗以及相关的心血管危险因素使这些人面临更高的风险过早发生心血管和肾脏疾病。项目3将研究糖尿病对糖尿病的调节作用新描述的细胞转运蛋白 ABCA1 在反向胆固醇转运中发挥着关键作用。从动脉壁清除胆固醇的能力缺陷会导致动脉粥样硬化的发生增加。项目4 将研究参与糖化和糖氧化反应的生化途径，这些反应在损害各种血管脂质和蛋白质，从而加速糖尿病的动脉粥样硬化。这些项目将得到一个行政核心和 2 个科学核心的支持：动脉组织和应用病理学核心将为其中 3 个项目提供来自糖尿病人类受试者和多种动物的动脉组织模型。蛋白质化学核心将为体外和体内提供复杂的生化支持所有项目中提出的研究。加深对血管性早发发病机制的了解每个项目产生的糖尿病疾病对以下疾病具有重要的治疗意义：糖尿病大血管疾病的预防和治疗。