Inflammation and Atherosclerosis in Rheumatoid Arthritis

类风湿性关节炎的炎症和动脉粥样硬化

• 批准号: 7919318
• 负责人: Ivy Ann Ku
• 金额: $ 6.22万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7919318
• 关键词: 3-nitrotyrosine; Animal Model; Arteries; Atherosclerosis; Biological Markers; Blood Vessels; C-reactive protein; Cardiac; Cause of Death; Chronic; Clinical; Cross-Sectional Studies; Development; Disease; Event; Functional disorder; General Population; Individual; Inflammation; Inflammatory; Joints; Left; Life; Lipoproteins; Measures; Mediating; N,N-dimethylarginine; Oxidative Stress; Patients; Protein C; Rheumatoid Arthritis; Risk; Risk Factors; Symptoms; Testing; United States; Vasodilation; cohort; human disease; improved; inflammatory marker; mortality; standard care; treatment strategy

DESCRIPTION (provided by applicant): Atherosclerosis and rheumatoid arthritis (RA) are two inflammatory diseases with marked similarities in pathobiology. In the general population, individuals with elevated inflammatory biomarkers (e.g. C- reactive protein, CRP) have increased CV events. Patients with RA have chronic elevations in CRP and other inflammatory markers that are usually higher than the levels associated with increased CV risk in the general population. Indeed, RA patients have accelerated atherosclerosis and increased CV mortality not explained by traditional cardiac risk factors but associated with chronic inflammation. However, the mechanisms by which systemic inflammation leads to atherosclerosis are not well characterized in RA. Moreover, current treatment strategies of RA largely target joint symptoms rather than systemic inflammation, potentially leaving patients at increased risk for CVD. In animal models and in human diseases, inflammation induces pro-atherogenic lipoprotein abnormalities, nitro-oxidative stress and endothelial dysfunction, which are pivotal in the development of atherosclerosis. However, studies of these pro-atherogenic markers in the full spectrum of inflammation and clinical manifestations in RA are missing. We hypothesize that inflammatory markers will be more strongly associated with atherogenic changes in RA patients than any clinical measure of disease activity. This hypothesis will be tested with a cross-sectional study of patients in the UCSF RA cohort. Aim 1 will characterize atherogenic changes across the spectrum of RA disease activity, specifically measuring endothelial function by flow-mediated vasodilation, markers of nitro-oxidative stress, and pro-atherogenic lipoproteins. Aim 2 will identify factors associated with these atherogenic changes across the spectrum of RA disease activity, specifically focusing on the association between inflammatory markers, FMD and pro-atherogenic lipoprotein abnormalities. Rheumatoid arthritis patients have increased inflammation in their bodies, which leads to atherosclerosis, or plaque build-up in blood vessels, the leading cause of death in the United States. By studying inflammation and atherosclerosis in RA, we can understand better what causes clogged arteries in general, as well as improve the standards of treatment for RA to prolong lives in addition to just alleviating symptoms.

描述（由申请人提供）：动脉粥样硬化和类风湿性关节炎（RA）是两种在病理生物学上具有显著相似性的炎性疾病。在一般人群中，炎症生物标志物（例如C反应蛋白，CRP）升高的个体CV事件增加。RA患者CRP和其他炎症标志物慢性升高，通常高于一般人群中与CV风险增加相关的水平。事实上，RA患者加速了动脉粥样硬化并增加了CV死亡率，这不能用传统的心脏危险因素来解释，而是与慢性炎症有关。然而，全身性炎症导致动脉粥样硬化的机制在RA中还没有很好的表征。此外，目前RA的治疗策略主要针对关节症状而不是全身炎症，可能会增加患者患CVD的风险。在动物模型和人类疾病中，炎症诱导促动脉粥样硬化脂蛋白异常、硝基氧化应激和内皮功能障碍，这些在动脉粥样硬化的发展中是关键的。然而，这些促动脉粥样硬化标记物在RA炎症和临床表现的全谱研究缺失。我们假设炎症标志物与RA患者的致动脉粥样硬化变化的相关性比任何疾病活动性的临床指标更强。这一假设将通过对UCSF RA队列患者的横断面研究进行检验。目的1将描述RA疾病活动范围内的致动脉粥样硬化变化，特别是通过血流介导的血管舒张、硝基氧化应激标志物和促动脉粥样硬化脂蛋白来测量内皮功能。目标2将确定与RA疾病活动范围内这些致动脉粥样硬化变化相关的因素，特别关注炎症标志物、FMD和促动脉粥样硬化脂蛋白异常之间的关联。风湿性关节炎患者体内炎症增加，导致动脉粥样硬化或血管中斑块积聚，这是美国死亡的主要原因。通过研究RA中的炎症和动脉粥样硬化，我们可以更好地了解导致动脉阻塞的原因，并提高RA的治疗标准，以延长生命，除了缓解症状。