Inflammation and Atherosclerosis in Rheumatoid Arthritis

描述(申请人提供)：动脉粥样硬化和类风湿关节炎(RA)是两种炎症性疾病，在病理生物学上有显著的相似之处。在一般人群中，炎性生物标志物(如C反应蛋白，CRP)升高的个体增加了心血管事件。类风湿性关节炎患者的CRP和其他炎症标志物的慢性升高通常高于普通人群中与心血管风险增加相关的水平。事实上，RA患者加速了动脉粥样硬化，增加了心血管死亡率，这不是传统的心脏危险因素所能解释的，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类风湿关节炎中还没有得到很好的描述。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，这可能会增加患者患CVD的风险。在动物模型和人类疾病中，炎症导致促动脉粥样硬化的脂蛋白异常、一氧化氮应激和内皮功能障碍，这些在动脉粥样硬化的发展中起着关键作用。然而，关于这些促动脉粥样硬化标志物在类风湿关节炎炎症和临床表现全谱中的研究尚不多见。我们假设炎性标记物与类风湿关节炎患者的动脉粥样硬化改变的相关性将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队列中的患者进行横断面研究来验证。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扩张、硝基氧化应激标志物和促致动脉粥样硬化的脂蛋白来测量内皮功能。目的2将通过RA疾病活动谱确定与这些致动脉粥样硬化改变相关的因素，特别侧重于炎症标志物、FMD和促致动脉粥样硬化脂蛋白异常之间的关联。类风湿性关节炎患者体内的炎症增加，这会导致动脉粥样硬化，或血管中的斑块堆积，这是美国的主要死亡原因。通过对RA炎症和动脉粥样硬化的研究，我们可以更好地了解导致动脉阻塞的一般原因，以及提高RA的治疗标准，在缓解症状的同时延长生命。

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.