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.

项目摘要/摘要 高血压（HTN）是心血管，脑血管和肾脏疾病的主要危险因素，其 患病率正在增加，尤其是在老年人中。虽然HTN的病理生理是多因素的 两个主要贡献者似乎是免疫系统的盐敏感性和激活。盛行 有关盐敏感HTN的范式基于血浆体积增加和静水力诱导 通过血管内钠保留。直到最近，几乎没有考虑到可能性 血管外钠店可能在HTN中发挥作用。通过使用新颖的非侵入性23NA-MAGNETIC 共振成像（MRI）技术，我们已经证明了存在明显的钠积累 在皮肤和骨骼肌中。实验证据表明，这些组织钠商店可以触发 免疫系统，特别是产生白介素17（IL17）的辅助T细胞（TH17）。这些T的激活 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 表明皮肤钠含量与收缩压有关。我们还发现循环IL17 与正常人相比，高血压的水平更高。但是，来自 需要更大的社区人群。动脉粥样硬化（MESA）的多民族研究是理想的队列 这可以翻译我们的初步发现。我们的基本假设是组织钠诱导的 炎症有助于HTN的发育和进展，尤其是对盐敏感的HTN。我们 提出一项辅助研究，其特定目的：1）定义组织Na+含量的分布 中年对社区中的老年人，2）研究组织钠水平的关联 血压和3）检查组织钠与TH17和其他细胞标记的关联 炎症。我们将使用23NA-MRI非侵入性地量化皮肤钠浓度并测量血液 在考试6（2016-2018）期间，所有合格的MESA参与者的压力。我们将 还量化了MESA参与者中循环免疫细胞的数量和类型，例如Th17细胞 谁接受了组织钠浓度的MRI测量。拟议的研究代表了一个独特的 利用大型，精心型的社区人口的机会，可以在其中翻译新颖的发现 从临床前和早期的人类研究，都可以更深入地了解病理生理学的贡献者 htn。拟议的研究代表了一个系统的努力，以基于调查人员的先前研究 HTN的基础机制以及组织钠，炎症和血液之间的新型相互作用 压力。这些研究有可能对HTN的决定因素提供重要的见解。 此外，由于MRI可视化组织钠是一种新型的非侵入性技术，因此确定了这一点 组织钠与炎症有关，HTN可以提出预防的新方法 HTN和相关疾病的治疗。