Tissue Sodium, Inflammation, and Blood Pressure in MESA

MESA 中的组织钠、炎症和血压

• 批准号: 9340012
• 负责人: Jens Marc Titze
• 金额: $ 74.53万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9340012
• 关键词: Acetates; Ancillary Study; Angiotensin II; Animal Model; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Biochemical; Biological Markers; Blood Plasma Volume; Blood Pressure; Body Water; CD4 Positive T Lymphocytes; Cardiovascular Diseases; Cells; Cerebrovascular Disorders; Chicago; Chronic Kidney Failure; Clinical; Clinical Trials; Collaborations; Communities; Country; Data; Deoxycorticosterone; Deposition; Development; Disease; Diuretics; Drug or chemical Tissue Distribution; Edema; Elderly; Eligibility Determination; Environment; Fibrosis; Flow Cytometry; Foundations; Functional disorder; Future; Heart Diseases; Heart failure; Helper-Inducer T-Lymphocyte; Human; Hypertension; Image; Imaging Techniques; Immune; Immune system; Immunologic Markers; Impairment; Individual; Inflammation; Inflammatory Response; Infusion procedures; Intake; Interleukin-17; Kidney Diseases; Lead; Linear Regressions; Link; Liver Failure; Magnetic Resonance Imaging; Measurement; Measures; Multi-Ethnic Study of Atherosclerosis; Muscle; Participant; Pathogenesis; Pharmaceutical Preparations; Phenotype; Physiology; Play; Population; Prevalence; Prevention approach; Recommendation; Regression Analysis; Research; Research Personnel; Resistant Hypertension; Role; Sampling Studies; Skeletal Muscle; Skin; Sodium; Sodium Chloride; Stroke; T-Lymphocyte; Techniques; Technology; Testing; Tissues; Transgenic Animals; Translating; Universities; Vasodilation; Vermont; Washington; Water; Work; World Health Organization; base; biomarker evaluation; blood pressure reduction; cardiovascular risk factor; circulating biomarkers; clinical application; cohort; cytokine; design; dietary salt; epidemiology study; experimental study; high risk; high salt diet; hypertension treatment; immune activation; inflammatory marker; insight; middle age; normotensive; novel; novel strategies; pre-clinical; response; salt intake; salt sensitive hypertension; tool; vascular inflammation

PROJECT SUMMARY/ABSTRACT Hypertension (HTN) is a major risk factor for cardiovascular, cerebrovascular, and renal disease, and its prevalence is increasing, particularly among the elderly. While the pathophysiology of HTN is multi-factorial, two major contributors appear to be salt-sensitivity and activation of the immune system. The prevailing paradigm regarding salt-sensitive HTN is based upon increased plasma volume and hydrostatic forces induced by intravascular sodium retention. Until recently, there was little consideration of the possibility that extravascular sodium stores may play a role in HTN. Through use of a novel non-invasive 23Na-magnetic resonance imaging (MRI) technique, we have demonstrated the presence of significant sodium accumulation in skin and skeletal muscle. Experimental evidence indicates that these tissue sodium stores can trigger the immune system, particularly the helper T cells (Th17) that produce interleukin-17 (IL17). Activation of these T cells and the cytokine they produce, IL17, induces HTN in animal models. In preliminary studies, we have shown that skin sodium content is associated with systolic blood pressure. We also found that circulating IL17 levels are higher in hypertensive compared with normotensive individuals. However, definitive data from larger, community cohorts are needed. The Multi-Ethnic Study of Atherosclerosis (MESA) is the ideal cohort in which to translate our preliminary findings. Our underlying hypothesis is that tissue sodium-induced inflammation contributes to the development and progression of HTN, particularly salt-sensitive HTN. We propose an ancillary study with the following specific aims: 1) to define the distribution of tissue Na+ content in middle-aged to elderly individuals in the community, 2) to investigate the association of tissue sodium levels with blood pressure, and 3) to examine the association of tissue sodium with Th17 and other cellular markers of inflammation. We will non-invasively quantify skin sodium concentration using 23Na-MRI and measure blood pressure in all eligible MESA participants at the Chicago, IL field center during exam 6 (2016-2018). We will also quantify the number and types of circulating immune cells, such as Th17 cells, among MESA participants who undergo MRI measurement of tissue sodium concentration. The proposed research represents a unique opportunity to leverage a large, well-phenotyped, community population in which to translate novel findings from preclinical and early human studies to gain a deeper understanding of pathophysiologic contributors to HTN. The proposed research represents a systematic effort to build upon the investigators' prior studies on the mechanisms underlying HTN and the novel interactions between tissue sodium, inflammation, and blood pressure. These studies have the potential to provide important insight into the determinants of HTN. Furthermore, because visualizing tissue sodium by MRI is a novel non-invasive technology, establishing that tissue sodium is associated with inflammation and HTN could suggest novel approaches to the prevention and treatment of HTN and related disorders.

项目概要/摘要 高血压（HTN）是心脑血管、肾脏疾病的主要危险因素，其 患病率正在增加，特别是在老年人中。虽然 HTN 的病理生理学是多因素影响的， 两个主要因素似乎是盐敏感性和免疫系统的激活。盛行的 关于盐敏感 HTN 的范例是基于增加的血浆体积和诱导的静水力 通过血管内钠潴留。直到最近，人们还很少考虑到这种可能性： 血管外钠储存可能在高血压中发挥作用。通过使用新型非侵入性 23Na 磁性 磁共振成像（MRI）技术，我们已经证明存在显着的钠积累 在皮肤和骨骼肌中。实验证据表明，这些组织钠储存可以触发 免疫系统，特别是产生白细胞介素 17 (IL17) 的辅助 T 细胞 (Th17)。激活这些T 细胞及其产生的细胞因子 IL17 在动物模型中诱导 HTN。在初步研究中，我们有 研究表明，皮肤钠含量与收缩压有关。我们还发现循环中的IL17 与血压正常的人相比，高血压患者的水平更高。然而，最终数据来自 需要更大的社区群体。动脉粥样硬化多种族研究 (MESA) 是动脉粥样硬化的理想队列 从而转化我们的初步发现。我们的基本假设是组织钠诱导 炎症有助于高血压（特别是盐敏感型高血压）的发生和进展。我们 提出一项具有以下具体目标的辅助研究：1）确定组织中 Na+ 含量的分布 社区中老年人，2) 调查组织钠水平的关联 与血压，以及 3) 检查组织钠与 Th17 和其他细胞标记物的关联 炎症。我们将使用 23Na-MRI 无创地量化皮肤钠浓度并测量血液 伊利诺伊州芝加哥现场中心所有符合资格的 MESA 参与者在考试 6（2016-2018 年）期间面临的压力。我们将 还量化 MESA 参与者中循环免疫细胞（例如 Th17 细胞）的数量和类型 接受 MRI 测量组织钠浓度的人。拟议的研究代表了独特的 有机会利用大量、表型良好的社区人群来转化新的发现 通过临床前和早期人体研究，深入了解病理生理学因素 HTN。拟议的研究代表了一项系统性的努力，以研究人员之前的研究为基础 高血压的机制以及组织钠、炎症和血液之间的新相互作用 压力。这些研究有可能为 HTN 的决定因素提供重要的见解。 此外，由于通过 MRI 可视化组织钠是一种新颖的非侵入性技术，因此确定 组织钠与炎症有关，HTN 可以提出预防和治疗炎症的新方法。 治疗高血压及相关疾病。