Study of Lupus Vascular and Bone Longterm Endpoints

狼疮血管和骨骼长期终点研究

• 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
• 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

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.

系统性红斑狼疮（SLE）是典型的全身性炎症性自身免疫性疾病， 主要影响绝经前的年轻女性。随着过去二十年生存率的提高， 越来越多患有SLE的年轻女性正在经历心血管（CVD）和心血管疾病（OP） 非SLE女性人群中通常与衰老相关的相关并发症。的发生 这些并发症仍然增加，即使在调整已知的传统风险因素和使用 皮质类固醇与这些并发症有关。宏观经济在启动和 动脉粥样硬化的进展和单核细胞或巨噬细胞是破骨细胞的前体， 导致骨质疏松症。我们的初步数据显示，在正常单核细胞的体外分化过程中， 在巨噬细胞中，大量对脂质代谢重要的基因上调， 运输，促进泡沫细胞的形成。此外，许多基因的表达上调 对破骨细胞的功能很重要，即使这些细胞不是破骨细胞。这五个方面的具体目标- 180名SLE和180名非SLE受试者的一项为期一年的纵向研究是1）在三个月内随访研究参与者 基线评估后5年和5年，以确定颈动脉、冠状动脉和 与年龄、种族和地理相似的非SLE对照组相比，SLE女性患者的主动脉粥样硬化，2） 检查巨噬细胞中脂质代谢基因表达谱，并将这些基因表达与 亚临床CVD的临床观察的基因表达谱，以及3）检查巨噬细胞中的基因表达谱 其在破骨细胞功能中具有潜在的重要性，并将这些基因表达谱与先前的 在腰椎和髋部测量的骨矿物质密度BMD的临床观察。的主要目标 本研究旨在验证亚临床和CVD的发生和进展增加， SLE妇女的OP标记物和事件与选定的 巨噬细胞中的生物途径或功能。将重点放在巨噬细胞作为参与 CVD和OP的病理生理学，并将巨噬细胞中基因上调的新数据与 在纵向队列中，仔细和广泛定义的表型，应该为 慢性炎症状态，易使SLE女性发生加速的CVD和OP。