The natriuretic peptide system in African-Americans

非裔美国人的利尿钠肽系统

• 批准号: 9270073
• 负责人: Deepak Gupta
• 金额: $ 18.42万
• 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: 2016-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9270073
• 关键词: Academic Medical Centers; Adult; African American; Area; Award; Blood Pressure; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cerebrovascular Disorders; ChIP-seq; Clinical Research; Crossover Design; Development; Disease; Disease susceptibility; Echocardiography; Enrollment; Excretory function; Future; Genetic; Genetic Variation; Goals; Heart; Heart Diseases; Heart failure; High Prevalence; Hormones; Human; Hypertension; Image; Imaging Techniques; Impairment; Individual; Intervention Studies; Investigation; Jackson Heart Study; K-Series Research Career Programs; Kidney; Lead; Left Ventricular Hypertrophy; Magnetic Resonance Imaging; Measures; Mediator of activation protein; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; National Heart, Lung, and Blood Institute; Natriuretic Peptides; Pathway interactions; Pharmacology; Phase; Physiological; Population; Positioning Attribute; Preventive; Principal Investigator; Race; Randomized; Renin-Angiotensin-Aldosterone System; Research; Research Activity; Research Infrastructure; Research Personnel; Resources; Rest; Risk; Sodium; Sodium Chloride; Standardization; Stimulus; Stress; Stroke; System; Techniques; Testing; Therapeutic; Tissues; Vasodilation; Work; admixture mapping; cardiovascular disorder risk; career; career development; circulating biomarkers; dietary salt; exome; exome sequencing; experience; genetic epidemiology; high risk; high salt diet; imaging biomarker; innovation; instructor; interest; normotensive; novel; patient oriented; prevent; programs; public health relevance; racial difference; racial disparity; research and development; response; salt sensitive; skills; success; urinary

 DESCRIPTION (provided by applicant): The applicant, Deepak K Gupta, MD is an Instructor of Medicine in the Division of Cardiovascular Medicine at Vanderbilt University Medical Center. The applicant's goal is to become a leading independent cardiovascular investigator with a research program focused on understanding mechanisms for the development of hypertension and related sequelae, particularly heart failure. This application for a K23 Mentored Patient- Oriented Research Career Development Award describes an integrated and tailored plan for the principal investigator to acquire the skills and unique expertise needed to transition into an independent investigator, under the primary mentorship of Thomas J Wang MD. The didactic and research activities proposed center on the study of the natriuretic peptide system in African-Americans. Hypertension is the major contributor to the development of cardiovascular disease, especially among African- Americans. Salt-sensitivity is regarded as an important mechanism for the development of hypertension among African-Americans; therefore, understanding the origins of salt-sensitivity has biologic, preventive, and therapeutic importance. The natriuretic peptide system is the principal counter-regulatory mechanism to salt retention; however, little is known regarding racial differences in the natriuretic peptide system. In preliminary work, we found that African-Americans have lower levels of circulating natriuretic peptides compared with whites, which may be in part due to genetic variation. Therefore, we postulate that African-American individuals can have a relative "natriuretic peptide deficiency," which predisposes to an impaired natriuretic peptide response to salt loading, increased salt-retention, and elevated blood pressure. The specific aims are (1) to assess the natriuretic peptide response to dietary salt loading in African-American individuals compared with white individuals, and (2) to examine the genetic basis for natriuretic peptide levels in African-Americans. During the course of the award period and through his study of the natriuretic peptide system in African- Americans, Dr. Gupta will acquire new expertise in 5 domains related to (1) patient-oriented physiologic studies, (2) pathophysiologic determinants of race-related differences in disease susceptibility, (3) genetic epidemiology, (4) the natriuretic peptide system, and (5) innovative techniques for measuring tissue sodium stores. The infrastructure at Vanderbilt for career development and scientific research is robust and uniquely capable of providing the resources that will promote the success of the proposed studies. Dr. Gupta's career development and research plans leverage his primary mentor's established record in human physiologic research related to the natriuretic peptide system. However, the targeted experiences will also provide a new direction for Dr. Gupta to develop into a leading investigator with unique expertise in the use of novel cardiac and non-cardiac imaging and circulating biomarkers for the study of hypertension and related sequelae, particularly in African-Americans. The results of the proposed studies will provide the basis for proposing and conducting new mechanistic and interventional studies in the next phase of the PI's career (i.e. R01) and therefore this Career Development Award would optimally prepare Dr. Gupta to lead his own independent clinical research program.

 描述（由申请人提供）：申请人 Deepak K Gupta，医学博士是范德比尔特大学医学中心心血管医学部的医学讲师。申请人的目标是成为一名领先的独立心血管研究者，其研究项目侧重于理解。高血压和相关后遗症（特别是心力衰竭）的发展机制 本 K23 指导性患者导向研究职业发展奖申请描述了一项为主要研究者获取技能和独特专业知识的综合且量身定制的计划。需要在托马斯·J·王医学博士的主要指导下转变为一名独立研究者。拟议的教学和研究活动集中在非裔美国人的利钠肽系统研究上。尤其是在非洲裔美国人中，盐敏感性被认为是非洲裔美国人患高血压的重要机制；因此，了解盐敏感性的起源具有生物学、预防和治疗的重要性。系统是盐潴留的主要反调节机制；然而，我们对利钠肽系统的种族差异知之甚少，我们发现非洲裔美国人的循环利钠肽水平低于白人，这可能是由于。因此，我们推测非洲裔美国人可能存在相对的“钠尿肽缺乏”，这导致钠尿肽对盐负荷的反应受损，盐潴留增加，具体目标是（1）与白人相比，评估非裔美国人对膳食盐负荷的利钠肽反应，以及（2）检查非裔美国人利钠肽水平的遗传基础。在获奖期间，通过对非裔美国人利尿钠肽系统的研究，Gupta 博士将获得 5 个领域的新专业知识，这些领域涉及 (1) 以患者为导向的生理学研究，(2) 疾病的病理生理学决定因素。与种族相关的疾病易感性差异，(3) 遗传流行病学，(4) 利尿钠肽系统，以及 (5) 测量组织钠储存的创新技术，范德比尔特大学用于职业发展和科学研究的基础设施非常强大，并且具有独特的能力。然而，提供资源将促进古普塔博士的职业发展和研究计划的成功，利用他的主要导师在利尿钠肽系统相关的人类生理研究方面的记录。为 Gupta 博士发展成为一名领先的研究者提供了新的方向，该研究人员在使用新型心脏和非心脏成像以及循环生物标志物来研究高血压和相关后遗症方面拥有独特的专业知识，特别是在非洲裔美国人中。为 PI 职业生涯下一阶段（即 R01）提出和开展新的机制和介入研究奠定了基础，因此该职业发展奖将为 Gupta 博士领导自己的独立临床研究项目做好最佳准备。