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HL146818-Uric Acid, Klotho and Salt Sensitivity in Young Adults Born Preterm

HL146818-早产青年的尿酸、Klotho 和盐敏感性

基本信息

批准号：
10175748
负责人：
MARK C CHAPPELL
金额：
$ 5.79万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-15 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10175748
关键词：
Address Admission activity Adult American American Heart Association Angiotensinogen Angiotensins Animals Antibodies Applications Grants Appointment Area Award Biochemical Biological Assay Biological Markers Biology Biomedical Research Biometry Birth Rate Blood Pressure Cardiology Cardiovascular Diseases Cardiovascular system Career Choice Cause of Death Cell physiology Cells Characteristics Clinical Clinical Sciences Co-Immunoprecipitations Collaborations Committee Members Communication Complement Computational Biology Critiques Data Data Analyses Development Doctor of Philosophy Ensure Enzyme-Linked Immunosorbent Assay Ethics Evaluation Event Exhibits Exposure to Extramural Activities Faculty Feedback Fellowship Foundations Frequencies Functional disorder Funding Future Goals Grant Graph Health Personnel Human Hypertension Inactive Renin Incidence Individual Infant Inflammation Inflammatory International Internships Journals Kidney Knowledge Laboratories Laboratory Research Lead Learning Life Link Literature Manuscripts Mass Spectrum Analysis Measures Medical Mentors Messenger RNA Metabolism Methods Microscopy Modeling Molecular Molecular Medicine Oral Organ Outcome Paper Pathology Pathway interactions Patients Peer Review Peptides Performance Pharmacologic Substance Pharmacology Phosphoproteins Physiology Postdoctoral Fellow Premature Birth Prevention Prevention strategy Process Proteins Proximal Kidney Tubules Publications Publishing Recording of previous events Regulation Renal tubule structure Renin Renin-Angiotensin System Reproducibility Research Research Activity Research Personnel Research Project Grants Research Proposals Research Training Resources Rest Risk Risk Factors Role Schools Scientist Series Signal Pathway Signal Transduction Slide Sodium Chloride Solid Students System TLR4 gene Techniques Time TimeLine Training Training Programs United States National Institutes of Health Universities Up-Regulation Update Uric Acid Western Blotting Work Writing analytical method anti aging base blood pressure regulation cardiovascular risk factor career career development cohort cytokine data integration emerging adult experience experimental study falls fetal fetal programming graduate student high risk high salt diet improved indexing innovation insight interest journal article lectures meetings member mid-career faculty novel therapeutics peer pre-doctoral preclinical study premature professor programs prorenin receptor response salt intake salt sensitive salt sensitive hypertension skill acquisition skills success summer research symposium treatment strategy undergraduate student university student uptake urinary young adult

项目摘要

ABSTRACT Hypertension is the leading risk factor for cardiovascular disease, is highly prevalent with high lifetime cumulative incidence rates, and is the leading cause of death compared to any other risk factor. Premature birth is an emerging and important risk factor for hypertension and cardiovascular disease, as both preterm birth rates and infant survival increase worldwide. Hypertension and cardiovascular disease begin in early adulthood in individuals born prematurely, but the reasons – especially in regard to the role of preterm birth – are unknown. An improved understanding of why hypertension and cardiovascular disease occur in early adulthood in individuals born preterm will enable the development of prevention and treatment strategies to mitigate the burden of cardiovascular disease. Salt sensitivity of blood pressure (SSBP; the change in blood pressure in response to a change in salt intake) is an emerging risk factor for hypertension and cardiovascular disease. However, little is known about the pathophysiology of SSBP, which limits its treatment and prevention. Individuals born preterm may be at higher risk for SSBP, but this too is unknown. Uric acid, which is higher in those born preterm due to altered uric acid metabolism, has been linked to development of SSBP in preclinical studies, but this concept has not been investigated in human trials. Uric acid may lead to SSBP via changes in klotho and the renin-angiotensin system, notably changes in the soluble prorenin receptor (sPRR) in the renal proximal tubules which has been linked to upregulation of Na+ transporters that may contribute to salt-sensitivity. Thus, the proposed study will determine the role of sPRR in this patient cohort and in human proximal tubule cells by the candidate. The diversity supplement serves as a robust and comprehensive training plan for the candidate graduate student includes the research plan involving the assessment of the sPRR in term and preterm adults maintained on a high salt diet, the role of Uric Acid on the regulation of sPRR in preterm salt-sensitive patients and the regulation of the sPRR in human proximal tubules and the functional and signaling characteristics of the sPRR. The mentoring team for the candidate is led by experienced and senior investigators with extensive experience in the preterm and term cohort, the influence of programing events on hypertension and internationally recognized expertise in the renin-angiotensin system and renal models of hypertensive disease. In addition to providing a comprehensive training plain that will ensure a strong foundation and pathway of the candidate to an independent investigator, the proposed research will establish the role of sPRR among individuals born preterm, thus providing evidence for the mechanisms behind the increased risk of hypertension and cardiovascular disease in individuals born prematurely.

摘要高血压是心血管疾病的主要危险因素，患病率高，寿命长累积发病率，并且与任何其他风险因素相比是死亡的主要原因。过早分娩是高血压和心血管疾病的一个新的重要危险因素，世界各地的出生率和婴儿存活率都在提高。高血压和心血管疾病开始于早产儿的成年，但原因-特别是在早产的作用方面， - 是未知的。更好地理解为什么高血压和心血管疾病发生在早产儿的早期成年将有助于预防和治疗的发展减轻心血管疾病负担的战略。血压的盐敏感性（SSBP; 盐摄入量的变化引起的血压变化）是高血压的一个新的危险因素和心血管疾病。然而，对SSBP的病理生理学知之甚少，这限制了其治疗。治疗和预防。早产的个体可能有较高的SSBP风险，但这也是未知的。由于尿酸代谢的改变，早产儿的尿酸水平较高， SSBP在临床前研究中的发展，但这一概念尚未在人体试验中研究。血尿酸可能通过klotho和肾素-血管紧张素系统的变化导致SSBP，特别是可溶性肾近端小管中的前肾素受体（sPRR）与Na+的上调有关可能导致盐敏感性的转运蛋白。因此，拟议的研究将确定sPRR的作用在该患者队列和人近端小管细胞中的表达。多样性补充服务于作为一个强大的和全面的培训计划，为候选人研究生包括研究计划包括在维持高盐饮食的足月和早产成人中评估sPRR，尿酸对早产儿盐敏感患者sPRR的调节及对早产儿sPRR的调节人近端小管和sPRR的功能和信号特征。指导团队对于候选人，由经验丰富的资深研究人员领导，和长期队列，高血压规划事件的影响和国际公认的专业知识在高血压疾病的肾素-血管紧张素系统和肾脏模型中。除了提供全面的培训平原，将确保一个坚实的基础和途径的候选人，独立调查员，拟议的研究将建立sPRR在出生于早产，从而为高血压风险增加背后的机制提供证据，早产儿的心血管疾病。