Neural and Renal Contributions to Hypertension with Androgen Deprivation Therapy

雄激素剥夺疗法对高血压的神经和肾脏影响

• 批准号: 10662133
• 负责人: Matthew C Babcock
• 金额: $ 16.62万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10662133
• 关键词: Accounting; Acute Renal Failure with Renal Papillary Necrosis; Adverse effects; Affect; Agonist; American; Androgen Receptor; Androgen Suppression; Androgens; Baroreflex; Biological Markers; Blood Pressure; Brain Stem; Cancer Survivor; Cancer Survivorship; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cause of Death; Cessation of life; Circulation; Clinical; Colorado; Data; Development Plans; Diagnosis; Distal; Doctor of Philosophy; Effectiveness; Environment; Exercise; Functional disorder; Funding; Future; Glomerular Filtration Rate; Goals; Gonadal Steroid Hormones; Gonadotropin Hormone Releasing Hormone; Growth; Heart Rate; Hormones; Human; Hypertension; IL18 gene; Impaired Renal Function; Impairment; Individual; Inflammation; Inflammatory; Interleukin-6; Isometric Exercise; Kidney; Kidney Diseases; LCN2 gene; Liver; Longitudinal Studies; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Medical; Medical Oncologist; Mentors; Mentorship; Metastatic Prostate Cancer; Microinjections; Nerve; Neuronal Dysfunction; Neurophysiology - biologic function; Observational Study; Outcome; Patients; Physiology; Placebo Control; Placebos; Population; Pre-Clinical Model; Prostate Cancer therapy; Proteomics; Randomized Controlled Clinical Trials; Rattus; Receptor Inhibition; Recording of previous events; Reflex action; Renal Blood Flow; Renal Plasma Flow; Renal function; Research; Research Design; Research Personnel; Resistance; Risk; Rodent; Role; Scientific Advances and Accomplishments; Secure; Survival Rate; System; Technical Expertise; Testing; Testosterone; Time; Training; Translating; Tubular formation; Universities; Vascular resistance; Work; androgen deprivation therapy; arm; aspirate; blood pressure control; blood pressure elevation; blood pressure regulation; blood pressure variability; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; career development; cytokine; experience; fatty acid-binding proteins; improved; inhibitor; insight; kidney dysfunction; kidney vascular structure; meetings; men; middle age; modifiable risk; mortality; multidisciplinary; neural; neural circuit; neuroregulation; older men; professor; prostate cancer survivors; rat KIM-1 protein; recruit; response; side effect; skills; vasoconstriction

PROJECT SUMMARY / ABSTRACT CANDIDATE: Matthew C. Babcock, Ph.D. is an Assistant Professor at the University of Colorado Anschutz Medical Campus (CU-AMC). Dr. Babcock aims to study the neural and renal contributions to hypertension with androgen deprivation therapy (ADT). He has developed preliminary data indicating that 1) men with lower testosterone concentrations have reduced baroreflex sensitivity compared to men with higher testosterone concentrations; and 2) baroreflex sensitivity in these individuals is correlated with circulating concentrations of the proinflammatory cytokine interleukin-6. In this proposal, he will translate these data by comprehensively assessing neural control of blood pressure in men who undergo ADT, and extend his observations to include renal control of blood pressure. The central hypothesis is that ADT increases inflammation and thereby reduces baroreflex sensitivity, increases sympathetic reactivity, and increases renovascular resistance. CAREER DEVELOPMENT PLAN: Dr. Babcock proposes to enhance his career development by: 1) acquiring new skills in the assessment of renal plasma flow, assessment of renal function biomarkers, and assessment of pro- inflammatory cytokines; 2) Advanced training renal diseases and physiology; 3) Working with a clinical population by recruiting men diagnosed with prostate cancer and studying them while they undergo ADT under the guidance of Dr. Elizabeth Kessler, a medical oncologist who specializes in prostate cancer; and 4) Refining his professional skills through formal course work, attendance and presentations at weekly Scientific Advancement and Grand Rounds, and at national scientific meetings. ENVIRONMENT: Dr. Babcock will train in an outstanding research environment supported by a multi-disciplinary team of mentors. The primary mentor, Dr. Moreau, is an NIA- funded professor at CU-AMC with a record of successful mentorship. She is an expert in the role of sex hormones and inflammation on cardiovascular function. She has extensive experience in utilizing the gonadal suppression study design proposed in the current study. Co-Mentor Dr. William Cornwell, III is also at CU-AMC and an expert in autonomic control of the circulation. Co-Mentor Dr. Jessica Kendrick and advisor Dr. Petter Bjornstad are also at CU-AMC and experts in studying renal function. Advisor Dr. Kessler is an expert in prostate cancer and ADT. Advisor Drs. Joyner and Farquhar are experts in autonomic function and the exercise pressor reflex. RESEARCH: ADT is a mainstay in the management of prostate cancer and the impressive survival rates among with men diagnosed with prostate cancer is largely attributed to the effectiveness of ADT. However, ADT increases the likelihood of developing hypertension and, accordingly, prostate cancer survivors who were treated with ADT are more likely to die early from cardiovascular diseases compared to men treated without the use of ADT. There is a critical need to elucidate the mechanisms underlying the increased cardiovascular disease risk in these patients to improve the lives of prostate cancer survivors.

项目概要/摘要 候选人：Matthew C. Babcock 博士是科罗拉多大学安舒茨分校的助理教授 医学校区（CU-AMC）。 Babcock 博士旨在研究神经和肾脏对高血压的影响 雄激素剥夺疗法（ADT）。他开发的初步数据表明 1) 男性的收入较低 与睾酮水平较高的男性相比，睾酮浓度降低了压力反射敏感性 浓度； 2）这些个体的压力反射敏感性与循环浓度相关 促炎细胞因子白细胞介素6。在这个提案中，他将综合翻译这些数据 评估接受 ADT 的男性血压的神经控制，并将他的观察结果扩展到包括 肾脏控制血压。中心假设是 ADT 会增加炎症，从而减少 压力反射敏感性，增加交感神经反应性，并增加肾血管阻力。职业 发展计划：Babcock 博士建议通过以下方式加强他的职业发展：1) 获取新技能 用于评估肾血浆流量、评估肾功能生物标志物以及评估亲 炎症细胞因子； 2）肾脏疾病和生理学进阶培训； 3) 与临床人群合作 招募被诊断患有前列腺癌的男性，并在他们在指导下接受 ADT 时对他们进行研究 伊丽莎白·凯斯勒 (Elizabeth Kessler) 博士是一位专门研究前列腺癌的肿瘤内科医生； 4）完善他的专业 通过正式课程作业、每周科学进步和盛大的出席和演讲来培养技能 查房和国家科学会议。环境：巴布科克博士将接受杰出研究的培训 由多学科导师团队支持的环境。主要导师 Moreau 博士是 NIA- CU-AMC 的资助教授，拥有成功的指导记录。她是性激素作用方面的专家 以及炎症对心血管功能的影响。她在利用性腺抑制方面拥有丰富的经验 当前研究中提出的研究设计。联合导师 William Cornwell, III 博士也是 CU-AMC 的专家 在循环的自主控制中。共同导师 Jessica Kendrick 博士和顾问 Petter Bjornstad 博士也是 CU-AMC 和研究肾功能的专家。顾问 Kessler 博士是前列腺癌和 ADT 方面的专家。 顾问博士。乔伊纳和法夸尔是自主功能和运动加压反射方面的专家。 研究：ADT 是前列腺癌治疗的支柱，其存活率令人印象深刻 男性诊断出患有前列腺癌的情况很大程度上归功于ADT的有效性。然而，ADT 增加患高血压的可能性，相应地增加接受治疗的前列腺癌幸存者 与未使用 ADT 治疗的男性相比，接受 ADT 治疗的男性更有可能因心血管疾病而提前死亡 ADT。迫切需要阐明心血管疾病风险增加的机制 在这些患者中改善前列腺癌幸存者的生活。