Non-classical cardiometabolic determinants of parathyroid hormone

甲状旁腺激素的非经典心脏代谢决定因素

基本信息

批准号：
9331351
负责人：
Sarah N Zaheer
金额：
$ 6.25万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9331351
关键词：
Abdomen Acute Adipose tissue Aldosterone Angiotensin II Angiotensin-Converting Enzyme Inhibitors Antihypertensive Agents Biochemical Markers Biological Blood Pressure Blood Volume Body fat Calcium Captopril Cardiovascular Diseases Cardiovascular system Clinical Research Clinical Sciences Cross-Sectional Studies Data Disease of parathyroid glands Environment Enzyme Inhibition Epidemiology Fatty acid glycerol esters Goals Hormones Hospitals Hour Human Hyperparathyroidism Hypertension Individual Infusion procedures Intervention Intervention Studies Investigation Knowledge Lead Link Lisinopril Measures Mediating Medical Mentors Metabolic Mineralocorticoid Receptor Modification Multi-Ethnic Study of Atherosclerosis Obesity PTH gene Patients Peptidyl-Dipeptidase A Pharmaceutical Preparations Physiological Population Prospective cohort Prospective cohort study Receptor Inhibition Recruitment Activity Renin-Angiotensin-Aldosterone System Research Research Training Scientist System Testing Training Translational Research Translations United States National Institutes of Health Vascular Diseases Visceral Vitamin D Deficiency Woman abdominal CT abdominal fat base cardiovascular risk factor catalyst clinical application clinical care clinical investigation clinically relevant epidemiologic data epidemiology study ethnic diversity inhibitor/antagonist interest men middle age mortality programs public health relevance skeletal disorder skills subcutaneous theories

项目摘要

DESCRIPTION (provided by applicant): The project proposed aims to investigate non-classical, cardiometabolic determinants of parathyroid hormone, with two specific aims: 1) to test the effect of acute and sustained use of ACE inhibition on parathyroid hormones (PTH) levels in healthy subjects and subjects with primary hyperparathyroidism, and 2) to investigate whether the association of PTH with adiposity is depot specific (i.e. driven by visceral adiposity) The context of these two aims arises from growing evidence supporting an interaction between PTH, a critical calcium-regulatory hormone, and the renin-angiotensin-aldosterone system (RAAS), which is a key regulator of blood pressure and volume status. In Aim 1, I will utilize knowledge of this interaction to test whether suppression of the RAAS by ACE inhibition causes a decrease in PTH in normal and primary hyperparathyroidism subjects. For this purpose, 20 normal subjects and 20 subjects with primary hyperparathyroidism will be recruited to perform an interventional study, testing calcium-regulatory markers, including PTH and calcium, and RAAS hormones levels before and after 1 hour and 1 week of treatment with commonly used ACE inhibitors, captopril and lisinopril, respectively. For Aim 2, a cross-sectional analysis will e performed using data from the Multi-Ethnic Study of Atherosclerosis (MESA), an ethnically diverse NIH- prospective cohort study of middle-aged men and women. Using demographic data, biochemical markers, and abdominal CT data, the association of PTH level with various abdominal adipose depots will be analyzed, adjusting for numerous confounders of PTH, to test for an independent association. In order to successfully achieve these goals, my research training plan includes training by my mentoring team (Dr. Gail Adler, Dr. Anand Vaidya, and Dr. Ian De Boer), and formal training in clinical investigation through the Harvard Catalyst Program for Clinical and Translational Science. In addition, my research environment at Brigham and Women's Hospital and the Harvard Catalyst is well-suited to allow successful completion of these aims.

描述（由申请人提供）：拟议的项目旨在研究甲状旁腺激素的非经典心脏代谢决定因素，有两个具体目标：1）测试急性和持续使用 ACE 抑制对甲状旁腺激素（PTH）水平的影响健康受试者和原发性甲状旁腺功能亢进症受试者，以及 2) 研究 PTH 与肥胖的关联是否具有仓库特异性（即由内脏肥胖驱动）这两者的背景目标源于越来越多的证据支持 PTH（一种重要的钙调节激素）与肾素-血管紧张素-醛固酮系统（RAAS）之间的相互作用，而肾素-血管紧张素-醛固酮系统是血压和容量状态的关键调节剂。在目标 1 中，我将利用知识。为了测试这种相互作用，ACE 抑制对 RAAS 的抑制是否会导致正常和原发性甲状旁腺功能亢进受试者的 PTH 降低。为此，将招募 20 名正常受试者和 20 名原发性甲状旁腺功能亢进受试者。进行一项介入研究，分别测试常用 ACE 抑制剂卡托普利和赖诺普利治疗前后 1 小时和 1 周的钙调节标志物（包括 PTH 和钙）以及 RAAS 激素水平，这是一项横断面研究。将使用动脉粥样硬化多种族研究 (MESA) 的数据进行分析，这是一项针对中年男性和女性的种族多元化 NIH 前瞻性队列研究，使用人口统计数据，生化标志物和腹部 CT 数据，将分析 PTH 水平与各种腹部脂肪库的关联，调整 PTH 的众多混杂因素，以测试独立关联。为了成功实现这些目标，我的研究培训计划包括培训。由我的指导团队（Gail Adler 博士、Anand Vaidya 博士和 Ian De Boer 博士）指导，并通过哈佛临床和转化科学催化剂计划进行正式的临床研究培训。此外，我的研究环境。布莱根妇女医院和哈佛催化剂非常适合成功实现这些目标。