Study of Lupus Vascular and Bone Longterm Endpoints

狼疮血管和骨骼长期终点研究

基本信息

批准号：
7665020
负责人：
Rosalind Ramsey-Goldman
金额：
$ 29.02万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7665020
关键词：
Address Adrenal Cortex Hormones Affect African American Age Aging Atherosclerosis Autoimmune Diseases Award Biological Blood Vessels Bone Density Bone Resorption Calcium Cardiovascular Diseases Cardiovascular system Caucasians Caucasoid Race Cells Chronic Clinical Complication Coronary Data Development Disease Disease Progression Electron Beam Tomography End Point Environment Event Foam Cells Follow-Up Studies Fracture Functional disorder Gene Expression Gene Expression Microarray Analysis Genes Goals Harvest Hip region structure Image Immune In Vitro Inflammation Inflammatory Laboratories Lesion Longitudinal Studies Lupus Lupus Erythematosus Measurement Measures Mediator of activation protein Molecular Profiling Monitor Myocardial Infarction Numbers Osteoclasts Osteoporosis Outcome Participant Pathogenesis Pathway interactions Patients Pattern Pharmaceutical Preparations Phenotype Play Population Premenopause RNA Race Rate Risk Factors Role Score Site Stroke Systemic Lupus Erythematosus Testing Thick Tissue-Specific Gene Expression Translational Research Ultrasonography Up-Regulation Vertebral column Woman bone cohort design experience improved indexing innovation insight intima media lipid metabolism macrophage monocyte peripheral blood programs

Address Adrenal Cortex Hormones Affect African American Age Aging Atherosclerosis Autoimmune Diseases Award Biological Blood Vessels Bone Density Bone Resorption Calcium Cardiovascular Diseases Cardiovascular system Caucasians Caucasoid Race Cells Chronic Clinical Complication Coronary Data Development Disease Disease Progression Electron Beam Tomography End Point Environment Event Foam Cells Follow-Up Studies Fracture Functional disorder Gene Expression Gene Expression Microarray Analysis Genes Goals Harvest Hip region structure Image Immune In Vitro Inflammation Inflammatory Laboratories Lesion Longitudinal Studies Lupus Lupus Erythematosus Measurement Measures Mediator of activation protein Molecular Profiling Monitor Myocardial Infarction Numbers Osteoclasts Osteoporosis Outcome Participant Pathogenesis Pathway interactions Patients Pattern Pharmaceutical Preparations Phenotype Play Population Premenopause RNA Race Rate Risk Factors Role Score Site Stroke Systemic Lupus Erythematosus Testing Thick Tissue-Specific Gene Expression Translational Research Ultrasonography Up-Regulation Vertebral column Woman bone cohort design experience improved indexing innovation insight intima media lipid metabolism macrophage monocyte peripheral blood programs

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项目摘要

Systemic lupus erythematosus (SLE) is the prototypic systemic inflammatory autoimmune disease that affects predominantly young premenopausal women. As survival has improved over the last two decades, increasing numbers of young women with SLE are experiencing cardiovascular (CVD) and osteoporotic (OP) related complications typically associated with aging in non-SLE populations of women. The occurrence of these complications remains increased, even after adjusting for known traditional risk factors and the use of corticosteroids associated with these complications. Macrophages play a critical role in the initiation and progression of atherosclerosis and monocytes or macrophages are precursors of osteoclasts, which contribute to osteoporosis. Our preliminary data shows during the in vitro differentiation of normal monocytes into macrophages there is upregulation of a large number of genes important for lipid metabolism and transport, which promote the formation of foam cells. Moreover, there is upregulation of many genes important for function of osteoclasts, even though these cells are not osteoclasts. The specific aims in this 5- year longitudinal study with 180 SLE and 180 non-SLE subjects are 1) to followup study participants at three years and five years after baseline assessment to determine the rate of progression of carotid, coronary, and aortic atherosclerosis in SLE women compared to age- race- and geographically-similar non-SLE controls, 2) examine lipid metabolism gene expression profiles in macrophages and relate these gene expression profiles to clinical observations of subclinical CVD, and 3) examine gene expression profiles in macrophages which are potentially important in osteoclast function and relate these gene expression profiles to previous clinical observations of bone mineral density, BMD, measured at the lumbar spine and hip. The main goal of this study is to test the hypothesis that the increased occurrence and progression of subclinical and CVD and OP markers and events in SLE women are associated with differential gene expression profiles of selected biological pathways or function in macrophages. Focusing on the macrophage as the key cell involved in the pathophysiology of both CVD and OP and merging the new data on gene upregulation in macrophages with a carefully and extensively defined phenotype, in a longitudinal cohort, should provide new insights into the chronic inflammatory state that predisposes women with SLE to develop accelerated CVD and OP.

全身性红斑狼疮（SLE）是原型的全身性炎症自身免疫性疾病影响年轻的年轻前女性。随着过去二十年来生存的提高，越来越多的年轻女性患有心血管（CVD）和骨质疏松症（OP）相关的并发症通常与非熟食女性衰老有关。出现这些并发症仍然增加，即使调整了已知的传统风险因素并使用与这些并发症相关的皮质类固醇。巨噬细胞在开始中起着至关重要的作用动脉粥样硬化和单核细胞或巨噬细胞的进展是破骨细胞的前体有助于骨质疏松症。我们的初步数据显示了正常单核细胞的体外分化进入巨噬细胞，有大量对脂质代谢重要的基因上调转运，促进泡沫细胞的形成。而且，许多基因都上调即使这些细胞不是破骨细胞，对于破骨细胞的功能很重要。这5-的具体目的使用180 SLE和180名非SLE受试者的年度纵向研究是1）跟进研究参与者基线评估后的年和五年，以确定颈动脉，冠状动脉和与年龄和地理位置相似的非SLE对照相比，SLE女性的主动脉动脉粥样硬化，2）检查巨噬细胞中的脂质代谢基因表达谱并关联这些基因表达对亚临床CVD的临床观察以及3）检查巨噬细胞中的基因表达谱图在破骨细胞功能中可能很重要，并将这些基因表达谱与以前的在腰椎和臀部测量的骨矿物质密度BMD的临床观察结果。主要目标这项研究是为了检验以下假设：亚临床和CVD的发生和进展增加 SLE女性的OP标记和事件与选定的差异基因表达谱有关巨噬细胞中的生物途径或功能。专注于巨噬细胞作为涉及的关键单元 CVD和OP的病理生理学以及合并有关巨噬细胞基因上调的新数据在纵向队列中，精心且广泛定义的表型应提供对该表型的新见解慢性炎症状态使患有SLE的妇女易于发展加速的CVD和OP。