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

• 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
• 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

 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）：该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抑制剂对健康受试者和原发性甲状旁腺功能亢进受试者的甲状旁腺激素（PTH）水平的影响，2）研究PTH与肥胖的关系是否具有储库特异性（即由内脏肥胖驱动）这两个目标的背景来自越来越多的证据支持PTH，一种关键的钙调节激素，以及肾素-血管紧张素-醛固酮系统（RAAS），它是血压和容量状态的关键调节器。在目标1中，我将利用这种相互作用的知识，以测试是否抑制RAAS的ACE抑制导致PTH在正常和原发性甲状旁腺功能亢进症受试者的减少。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干预性研究，分别检测常用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）和RAAS激素水平。对于目标2，将使用来自动脉粥样硬化多种族研究（梅萨）的数据进行横断面分析，MESA是一项针对中年男性和女性的种族多样性NIH前瞻性队列研究。使用人口统计学数据、生化标志物和腹部CT数据，分析PTH水平与各种腹部脂肪蓄积的相关性，调整PTH的众多混杂因素，以检验独立相关性。为了成功实现这些目标，我的研究培训计划包括由我的指导团队（Gail Adler博士、Anand Vaidya博士和Ian De Boer博士）进行的培训，以及通过哈佛临床和转化科学催化剂计划进行的临床研究正式培训。此外，我在布里格姆妇女医院和哈佛催化剂的研究环境非常适合成功完成这些目标。