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医学的讲师。申请人的目标是成为一名领先的独立心血管研究者，研究计划的重点是理解高血压和相关后遗症的机制，尤其是心力衰竭。这项针对K23指导的以患者为导向的研究职业发展奖的申请描述了一项综合和量身定制的计划，该计划在Thomas J Wang MD的主要思想下，为了获得过渡到独立研究者所需的技能和独特的专业知识。教义和研究活动提出了关于非裔美国人纳特里尔酸肽系统研究的中心。高血压是心血管疾病（尤其是在非裔美国人）发展的主要因素。盐敏感被认为是非裔美国人中高血压发展的重要机制。因此，了解盐敏的起源具有生物学，预防和治疗意义。亚钠肽系统是保留盐的主要反调节机制。然而，关于纳地钠肽系统的种族差异知之甚少。在初步工作中，我们发现与白人相比，非裔美国人的循环发作肽的水平较低，这可能部分是由于遗传变异。因此，我们假设非洲裔美国人可以具有相对的“纳地酸肽缺乏症”，这易于降低脂肪肽对盐负荷的反应受损，脂肪升高和血压升高。具体目的是（1）与白人个体相比，评估非裔美国人个体中饮食中饮食盐负荷的亚钠肽反应，以及（2）检查非裔美国人纳特三钠肽水平的遗传基础。在奖励期间，通过对非裔美国人的纳特里尔氨基肽系统的研究，Gupta博士将获得与（1）面向患者的生理学研究有关的5个领域的新专业知识，（2）病理生理生理学的确定剂，在疾病临床中与种族相关差异的差异，（3）遗传Epetive Intrice and（3）NATIRE（3）NATRII，（4），（4）（4）测量组织钠储存的技术。范德比尔特（Vanderbilt）的职业发展和科学研究的基础设施具有强大的和独特的能力，能够提供促进拟议研究成功的资源。 Gupta博士的职业发展和研究计划利用了他的主要心态在与Natriaretic肽系统有关的人类生理研究中建立了记录。但是，有针对性的体验还将为Gupta博士提供一个新的方向，使其发展成为一名具有独特专业知识的领先研究者，该研究人员在使用新颖的心脏和非心脏成像和循环生物标志物中用于研究高血压和相关后遗症，尤其是在非裔美国人中。拟议研究的结果将为PI职业生涯的下一阶段（即R01）提出和进行新的机械和介入研究的基础，因此，该职业发展奖将最佳地准备Gupta博士领导自己的独立临床研究计划。