Race, Natriuretic Peptides and Physiological Perturbations

种族、利尿钠肽和生理干扰

• 批准号: 10397576
• 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/10397576
• 关键词: Adipose tissue; Adrenergic beta-Antagonists; Adult; African American; African American population; 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; 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; antagonist; cardiovascular disorder risk; cardiovascular health; collaborative environment; community engagement; 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.

项目总结/摘要 申请人Pankaj Arora医学博士是心血管科的医学助理教授， 疾病在伯明翰的亚拉巴马大学。申请人的目标是成为独立的 临床和转化研究的调查员，并促进对疾病如何在 利钠肽（NP）系统参与高血压、心力衰竭和心血管疾病的发生发展 疾病申请人已经表现出对理解遗传学、NP系统生物学和 进行高质量的以患者为导向的研究的能力。这种指导性的以患者为导向的研究生涯 发展奖（K23）描述了一个五年计划，将允许申请人实现独立， 一名研究员，在托马斯J.王医学博士的主要指导下，他是国际公认的 NP生理学申请人希望获得4个特定领域的知识和专业知识：（1） 以患者为导向的生理学研究，（2）心血管种族相关差异的病理生理基础 疾病易感性，（3）运动生理学，和（4）面向患者的药理学研究。 非裔美国人心血管疾病的患病率增加，这导致了种族差异 死亡和住院治疗等结果。NPs是利钠利尿激素和血管舒张激素， 心脏对心房和心室壁应力增加的反应。在这项提案的初步工作中， 我们发现非裔美国人与NP缺乏有关。关于生理学的知之甚少 非裔美国人中发现的较低静息NP水平的后果。目前的建议将寻求 确定心脏对生理扰动的反应是否存在种族差异， 锻炼和β受体阻滞剂具体目的是（1）比较非洲人对β受体阻滞剂的NP反应- 美国人和白色人（2）比较非裔美国人和白色人对运动的NP反应 个体理解这些NP释放的差异可能具有生物学和治疗学意义。 在高血压和心力衰竭治疗中的重要性。 指导以患者为导向的研究职业发展奖（K23）将为Arora博士提供 充分参与多方面的、精心设计的以患者为导向的研究方案所需的时间， 作为接受额外的正式教学的手段。在授标期间，申请人 我将在UAB的公共卫生学院攻读临床与转化科学的公共卫生硕士学位 健康，以提高他在以病人为导向的研究（流行病学，生物统计学，研究设计，补助金- 写作和领导力课程）。UAB丰富的协作，跨学科的环境与国家 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。拟定的研究将为研究者设计和实施 在特定人种亚组中进行干预性研究（例如R 01），以个性化现有和新型治疗方法 在NP系统中。