Race, Natriuretic Peptides and Physiological Perturbations

种族、利尿钠肽和生理干扰

• 批准号: 9900851
• 负责人: Pankaj Arora
• 金额: $ 19.38万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9900851
• 关键词: Adipose tissue; Adrenergic beta-Antagonists; Adult; African American; Alabama; Atrial Natriuretic Factor; Award; Biological; Biological Response Modifier Therapy; Biometry; Brain natriuretic peptide; Cardiovascular Diseases; Cardiovascular system; Cerebrovascular Disorders; Cessation of life; Classification; Clinical Research; Clinical Sciences; Collection; Communities; Development; Diet; Disease; Disease susceptibility; Enrollment; Epidemiology; Ethics; Excretory function; Exercise; Exercise Physiology; Five-Year Plans; Funding; Genetic; Genetic Markers; Goals; Grant; Guanosine Monophosphate; Heart; Heart Atrium; Heart failure; High Prevalence; Hormones; Hospitalization; Human; Hypertension; Impairment; Individual; International; Intervention; Intervention Studies; Kidney; Knowledge; Leadership; Master of Science; Measures; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Metabolic; Metabolism; Methods; Metoprolol; Metoprolol Succinate; N-terminal; Natriuretic Peptides; Outcome; Oxygen; Participant; Patients; Periodicity; Pharmaceutical Preparations; Pharmacology; Pharmacology Study; Physiological; Physiology; Prevalence; Principal Investigator; Production; Protocols documentation; Public Health; Public Health Schools; Race; Renin-Angiotensin-Aldosterone System; Research; Research Design; Research Personnel; Rest; Skeletal Muscle; Sodium; Sodium Chloride; Specimen; Standardization; Stress; Subgroup; System; Systems Biology; Testing; Thinness; Time; Training; Translational Research; Underrepresented Minority; Universities; VO2max; Vasodilation; Work; Writing; cardiovascular disorder risk; cardiovascular health; collaborative environment; design; efficacy testing; experience; genetic testing; health disparity; hemodynamics; hypertension treatment; insight; interest; new therapeutic target; normotensive; novel therapeutics; patient oriented; patient oriented research; personalized medicine; physiologic stressor; primary endpoint; professor; programs; racial and ethnic disparities; racial difference; racial disparity; recruit; response; secondary endpoint; skills; social; social health determinants; uptake; urinary; valsartan

PROJECT SUMMARY/ABSTRACT The applicant, Pankaj Arora, MD is an Assistant Professor of Medicine in the Division of Cardiovascular Disease at University of Alabama at Birmingham. The applicant’s goal is to become an independent investigator in clinical and translational research and advance the understanding of how disorders in the natriuretic peptide (NP) system contribute to the development of hypertension, heart failure and cardiovascular disease. The applicant has shown a prior interest in understanding the genetics, NP system biology and an ability to conduct high-quality patient-oriented research. This Mentored Patient-Oriented Research Career Development Award (K23) describes a five-year plan that will allow the applicant to achieve independence as an investigator, under the primary mentorship of Thomas J. Wang MD, an internationally-recognized leader in the field of NP physiology. The applicant wishes to obtain knowledge and expertise in 4 specific domains: (1) patient-oriented physiologic studies, (2) the pathophysiologic basis of race-related differences in cardiovascular disease susceptibility, (3) exercise physiology, and (4) patient-oriented pharmacologic studies. African-Americans have increased prevalence of cardiovascular disease which contributes to racial disparities in outcomes such as death and hospitalization. NPs are natriuretic and vasodilatory hormones produced by the heart in response to increased wall stress in the atria and ventricles. In preliminary work for this proposal, we found that African-American race is associated with NP deficiency. Little is known about the physiological consequences of the lower resting NP levels found in African-Americans. The current proposal will seek to determine if there exists racial differences in how the heart responds to physiological perturbations such as exercise and beta blockers. The specific aims are (1) To compare the NP response to beta blockers in African- American and white individuals (2) To compare the NP response to exercise in African-American and white individuals. Understanding these differences in release of NPs may have biological and therapeutic importance in the treatment of hypertension and heart failure. The Mentored Patient-Oriented Research Career Development award (K23) will provide Dr. Arora with the necessary time to fully engage in multifaceted, carefully designed patient-oriented research protocols while serving as a means to receive additional formal didactics. During the course of the award period, the applicant will pursue a Master of Science in Public Health in Clinical & Translational Science at UAB’s School of Public Health to advance his skills in patient-oriented research (epidemiology, biostatistics, study design, grant- writing, and leadership courses). UAB’s rich collaborative, interdisciplinary environment with national recognition for community engagement will provide Dr. Arora with a platform to successfully conduct the research proposed in the plan. The proposed studies will prepare the investigator to design and conduct interventional studies (e.g. R01) in specific racial subgroups to personalize existing and novel therapeutics around the NP system.

项目摘要/摘要 申请人Pankaj Arora医学博士是心血管科医学助理教授 阿拉巴马大学伯明翰分校的疾病。申请者的目标是成为一名独立的 临床和转化性研究的调查员，并促进对精神障碍是如何 利钠肽(NP)系统参与高血压、心力衰竭和心血管疾病的发展 疾病。申请人对遗传学、NP系统生物学和 能够进行高质量的以患者为中心的研究。指导了以患者为中心的研究生涯 发展奖(K23)描述了一个五年计划，该计划将允许申请者实现独立，如 一名调查员，在托马斯·J·王医学博士的主要指导下，他是国际公认的 NP生理学领域。申请人希望获得4个具体领域的知识和专业知识：(1) 以病人为中心的生理学研究，(2)心血管疾病种族差异的病理生理学基础 疾病易感性，(3)运动生理学，(4)以病人为中心的药理学研究。 非裔美国人心血管疾病患病率增加，这是造成种族差异的原因之一 死亡和住院等后果。NPS是一种利钠和扩张血管的激素，由 心脏对心房和心室壁应力增加的反应。在这项提案的前期工作中， 我们发现非裔美国人与NP缺乏症有关。对生理学知识知之甚少 在非裔美国人中发现较低的静息NP水平的后果。目前的提案将寻求 确定心脏对生理干扰的反应方式是否存在种族差异 运动和β-受体阻滞剂。具体目的是(1)比较非洲地区NP对β受体阻滞剂的反应。 美国人和白人个人(2)比较非裔美国人和白人对运动的NP反应 个人。了解这些NPs释放的差异可能具有生物学和治疗作用 在治疗高血压和心力衰竭方面的重要性。 以患者为导向的导师研究职业发展奖(K23)将为阿罗拉博士提供 充分参与多方面、精心设计的以患者为导向的研究方案所需的时间，同时 作为接受额外正式教学的一种手段。在授权期内，申请人 将在UAB公共学院攻读临床和转化学公共卫生理学硕士学位 提高他在以病人为中心的研究(流行病学、生物统计学、研究设计、赠款-- 写作和领导力课程)。UAB丰富的协作、跨学科环境与国家 对社区参与的认可将为阿罗拉博士提供一个成功开展 计划中提出的研究。拟议的研究将使调查员准备好设计和实施 对特定种族亚群进行干预研究(例如R01)，使现有和新的治疗方法个人化 围绕着NP系统。