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HDL and cardiovascular risk in chronic kidney disease

高密度脂蛋白和慢性肾脏病的心血管风险

基本信息

批准号：
8517181
负责人：
ANDREW N HOOFNAGLE
金额：
$ 36.77万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8517181
关键词：
Activities of Daily Living Adult Aerobic Exercise Affect American Americas Anti-Inflammatory Agents Anti-inflammatory Antiatherogenic Applications Grants Atherosclerosis Attenuated Biological Assay Biological Preservation Blood Vessels Cardiac Cardiovascular Diseases Cardiovascular system Cause of Death Cell physiology Cells Cessation of life Cholesterol Chronic Kidney Failure Clinical Clinical Data Clinical Research Cohort Studies Data Development Diet Disease Pathway Disease Progression End stage renal failure Endothelial Cells Endothelium Event Freedom Functional disorder Funding Future General Population Glomerular Filtration Rate Goals Health High Density Lipoproteins High Prevalence In Vitro Individual Inflammation Intervention Investigation Kidney Kidney Diseases Kidney Failure Laboratories Lead Low-Density Lipoproteins Measures Methods Molecular Myocardial Infarction National Heart, Lung, and Blood Institute National Institute of Diabetes and Digestive and Kidney Diseases Nonesterified Fatty Acids Outcome Oxidative Stress Pathway interactions Patients Persons Phenotype Population Property Proteins Public Health Randomized Controlled Trials Renal function Research Institute Risk Risk Factors Staging Stroke United States United States National Institutes of Health Vasodilation base cardiovascular disorder risk cardiovascular risk factor design diet and exercise high risk improved in vivo inorganic phosphate lifestyle intervention macrophage new therapeutic target novel particle treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Nearly one in every seven adults in America has chronic kidney disease (CKD), representing a 30% increase in the past decade. Individuals with advanced CKD are at extraordinarily high risk for loss of kidney function, cardiovascular events, and death, and cardiovascular disease is the leading cause of death in people with CKD. While much is unknown about why cardiovascular risk in individuals with CKD is so high, we and others have demonstrated that CKD is associated with increased systemic inflammation, elevated free fatty acids, and oxidative stress that lead to dysfunction of the endothelium. We and others have shown that high density lipoproteins (HDL) contain factors that reduce the level of activation and dysfunction of endothelial cells in vitro. Moreover, there is evidence that HDL from patients with CKD is altered in composition and function, which may directly cause endothelial dysfunction and lead to atherosclerosis and worsening kidney function. We have developed novel mass spectrometric methods to assess HDL composition and cell-based assays to assess the ability of HDL to preserve endothelial cell function. The combination of these assays provides for a comprehensive investigation of the molecules that contribute to HDL's anti-inflammatory capacity. Our overall hypothesis is that CKD causes changes to HDL composition and that these changes lead to increased endothelial dysfunction and greater risk of glomerular loss and cardiovascular disease (CVD). We also hypothesize that diet and exercise, an intervention that improves endothelial function in vivo, will lead to beneficial changes in HDL composition. Our goal is therefore to better understand the association of changes in HDL composition and function with endothelial dysfunction and clinical outcomes. We will take advantage of three well-characterized, NIH-funded clinical studies to elucidate the mechanisms behind HDL's ability to preserve endothelial cell function. To achieve these objectives, we propose the following aims: 1) Comprehensively characterize HDL composition and function in the CKD population; 2) Identify and quantify the changes in HDL composition and function that are associated with cardiac events, progression of kidney disease, and death; and 3) Determine whether healthy lifestyle interventions modify HDL composition and restore its anti-inflammatory properties in CKD subjects. This proposal will identify the molecular changes in HDL in subjects with CKD and how they are associated with endothelial dysfunction in vitro and in vivo. Moreover, our studies will identify the changes in HDL composition that are associated with cardiovascular and renal outcomes in a population at greatly increased risk of death.