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，医学博士是心血管司的医学助理教授 伯明翰阿拉巴马大学的疾病。申请人的目标是成为独立 研究人员在临床和翻译研究方面，并促进了对疾病的理解 亚钠肽（NP）系统有助于高血压，心力衰竭和心血管的发展 疾病。申请人对了解遗传学，NP系统生物学和 能够进行高质量的以患者为导向的研究。这项指导的以患者为导向的研究职业 发展奖（K23）描述了一项五年计划，该计划将使申请人获得独立性 在国际公认的领导人托马斯·J·王（Thomas J. Wang MD）的主要心态下的调查员 NP生理学领域。适当的希望获得4个特定领域的知识和专业知识：（1） 面向患者的生理学研究，（2）与种族相关的心血管差异的病理生理基础 疾病敏感性，（3）运动生理学和（4）面向患者的药物研究。 非裔美国人的心血管疾病患病率增加了，这有助于种族分布 在死亡和住院等结果中。 NP是纳地尿剂和血管舒张恐怖。 心脏和心室中壁应力增加的心脏。在此提案的初步工作中， 我们发现非裔美国人种族与NP缺乏症有关。关于生理学知之甚少 在非裔美国人中发现的较低静息NP水平的后果。当前的提议将寻求 确定在心脏对身体扰动的反应方式上是否存在种族差异，例如 运动和β受体阻滞剂。具体目的是（1）将NP响应与非洲的β受体阻滞剂进行比较 美国和白人个人（2）比较非裔美国人和白人运动的NP反应 个人。了解这些在NP的释放方面的差异可能具有生物学和治疗性 在治疗高血压和心力衰竭方面的重要性。 受过指导的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，精心设计的以患者为导向的研究协议的必要时间 作为接收其他正式教学的手段。在奖励期间，适用 将攻读UAB公共学院临床与转化科学公共卫生科学硕士学位 健康以提高他在以患者为导向的研究方面的技能（流行病学，生物统计学，研究设计，授予 - 写作和领导课程）。 UAB与国家的丰富合作，跨学科环境 认可社区参与将为Arora博士提供成功进行的平台 计划中提出的研究。拟议的研究将使研究人员准备设计和进行 介入研究（例如R01）在特定种族亚组中，以个性化现有和新颖的疗法 在NP系统周围。