Study of Lupus Vascular and Bone Longterm Endpoints

系统性红斑狼疮(SLE)是一种典型的全身性炎症性自身免疫病 主要影响年轻的绝经前妇女。在过去的二十年里，随着存活率的提高， 越来越多的患有系统性红斑狼疮的年轻女性正在经历心血管疾病(CVD)和骨质疏松(OP) 在非系统性红斑狼疮女性人群中，相关并发症通常与年龄有关。事件的发生 即使在对已知的传统风险因素进行调整并使用 与这些并发症有关的皮质类固醇。巨噬细胞在启动和释放过程中起关键作用。 动脉粥样硬化的进展和单核或巨噬细胞是破骨细胞的前体细胞，其中 导致骨质疏松症。我们的初步数据显示，在正常单核细胞体外分化过程中 巨噬细胞中有大量对脂类新陈代谢和 运输，促进泡沫细胞的形成。此外，还有许多基因的上调。 对破骨细胞的功能很重要，即使这些细胞不是破骨细胞。这5项措施的具体目标是： 对180名系统性红斑狼疮和180名非系统性红斑狼疮受试者进行为期一年的纵向研究：1)对研究参与者进行三年的随访 在基线评估后五年和五年，以确定颈动脉、冠状动脉和 SLE女性的动脉粥样硬化与年龄、种族和地理位置相似的非SLE对照组的比较，2) 检测巨噬细胞脂代谢基因表达谱及与这些基因表达的关系 亚临床CVD的临床观察；3)巨噬细胞基因表达谱 它们在破骨细胞功能中具有潜在的重要作用，并将这些基因表达谱与以前的 腰椎和髋部骨密度测量的临床观察。的主要目标是 这项研究旨在检验以下假设：亚临床和心血管疾病的发生和进展增加， 系统性红斑狼疮患者的OP标志物和事件与所选基因表达谱差异相关 巨噬细胞的生物学途径或功能。重点关注巨噬细胞作为参与 CVD和OP的病理生理学及合并巨噬细胞基因上调的新数据 一个仔细而广泛定义的表型，在纵向队列中，应该提供对 慢性炎症状态，使SLE女性更容易发生加速的心血管疾病和OP。

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.