Project 1.Stress and African American Male Predisposition for Kidney and Cardiometabolic Disease

项目 1.压力与非洲裔美国男性肾脏和心脏代谢疾病的易感性

• 批准号: 10204737
• 负责人: Mildred Audrey Pointer
• 金额: $ 29.3万
• 依托单位: NORTH CAROLINA CENTRAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-20 至 2022-09-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10204737
• 关键词: African American; Age; Age-Years; Albumins; Aldosterone; Analysis of Variance; Anger; Animal Model; Animals; Biological; Biological Markers; Blood; Blood Pressure; Body mass index; Buffers; Cardiometabolic Disease; Cessation of life; Corticosterone; Corticotropin; Creatinine; Cross-Sectional Studies; Data; Death Rate; Development; Disease; Education; Electrolytes; Evaluation; Excretory function; Exposure to; Female; Fibrosis; Functional disorder; Gender; Glomerular Filtration Rate; Glucose; Glycosylated hemoglobin A; Goals; Health; Histopathology; Hormones; Hostility; Human; Hydrocortisone; Hypertension; Hypothalamic structure; Income; Inflammation; Injury to Kidney; Insulin; Kidney; Kidney Diseases; Lead; Life Expectancy; Link; Lipids; Malignant Neoplasms; Measurement; Measures; Methods; Mineralocorticoid Receptor; Modeling; Mus; Myocardial Infarction; Nerve; Output; Participant; Perception; Pituitary-Adrenal System; Plasma; Play; Predisposition; Prevalence; Process; Renin; Research; Research Design; Resources; Risk; Role; Sampling; Serum; Signal Pathway; Social support; Stress; Surveys; System; Tail; Telemetry; Testing; Time; Urine; Vulnerable Populations; Woman; base; cardiometabolism; cohort; cooking; coping; disease disparity; disorder risk; experience; health disparity; insight; kidney dysfunction; male; male health; mortality; mouse model; nephrogenesis; perceived stress; prevent; psychosocial; racism; recruit; renal damage; response; salt sensitive hypertension; sex; social; socioeconomics; stressor; urinary

ABSTRACT Young hypertensive African American (AA) males have a 10 to 14-fold greater risk for kidney disease than any other hypertensive group. The reason for this striking disparity remains unknown. What is known is that racism significantly contributes to disease risk in AAs. Our preliminary results suggest that the stress hormone system is activated in AA males in association with perceived racism but not in AA females. These findings raise the questions: why do AA males' experiences of racism result in activation of the hypothalamus-pituitary-adrenal axis (HPA) system and how are AA males and females different in their biological response to perceived racism (PR)? This project proposes to investigate these important questions. The conventional conceptual frame for racism and disease suggests that maladaptive coping methods in perception of stress and in response to racism or stress in general can promote the activation of the HPA system while adaptive methods may mititgate the HPA activation. Therefore, we posit that the AA male health disparity may result from use of maladaptive coping methods that leads to activation of the HPA resulting in increased stress hormones aldosterone (ALDO) and cortisol and sympathetic nerve output, both of which promote cardiorenal diseases. ALDO is known to: be elevated in kidney disease; be higher in AAs; and promote kidney injury in the setting of salt-sensitive hypertension by activating the mineralocorticoid receptor (MR) resulting in subsequent inflammation and fibrosis development through RAC 1 pathway signaling. Thus, ALDO is a stress hormone that likely plays a major role in the kidney disease disparity in this vulnerable group. To test our hypothesis we will recruit AA males and females and administer psychosocial surveys to determine their perceived racism and stress levels; their use of maladaptive coping (anger and hostility); their use of adaptive coping (social support); and their levels of ALDO and cortisol. We will determine whether adaptive coping acts to buffer the increase in ALDO and cortisol while maladaptive coping promotes the increase in ALDO and cortisol levels. Furthermore, we will determine if the ALDO and cortisol levels are associated with increased risk for kidney injury in AAs. We also use animal model to confirm that increased ALDO and cortisol can cause kidney damage in the setting of hypertension. The results from this study will be the first to show the underlying pathophysiology (ALDO) link between racism and kidney disease and, consequently, provide new insights that could lead to more precise treatment of AA for hypertension that will prevent the development of kidney disease that is often associated with hypertension.

抽象的 年轻的高血压非裔美国人（AA）男性患肾脏疾病的风险比任何人高10至14倍 其他高血压组。这种惊人的差距的原因仍然未知。众所周知的是种族主义 大大导致AAS疾病风险。我们的初步结果表明应力激素系统 在AA男性中被激活，与感知的种族主义相关，但没有在AA女性中激活。这些发现提出了 问题：为什么AA男性的种族主义经历会激活下丘脑 - 垂体 - 肾上腺 轴（HPA）系统以及AA雄性和女性在对感知的生物学反应中如何不同 种族主义（PR）？该项目建议调查这些重要问题。传统的概念 种族主义和疾病的框架表明，在压力感知和中，适应不良的应对方法 对种族主义或压力的反应通常可以促进HPA系统的激活，而自适应方法 可能会缓解HPA激活。因此，我们认为AA男性健康差异可能是由于使用 适应性应对方法导致HPA激活，导致应力激素增加 醛固酮（Aldo）和皮质醇和交感神经输出，两者都会促进心脏疾病。 众所周知，阿尔多（Aldo）在肾脏疾病中升高；在AAS中更高；并在环境中促进肾脏受伤 盐敏感的高血压通过激活盐皮质激素受体（MR），导致随后的 通过RAC 1途径信号传导的炎症和纤维化发展。因此，阿尔多是一种应力激素 在这个脆弱的群体中，这可能在肾脏疾病差异中起着重要作用。为了检验我们的假设我们 将招募AA男性和女性，并管理社会心理调查以确定他们的种族主义 和压力水平；他们使用适应不良的应对（愤怒和敌意）；他们使用适应性应对（社会 支持）;以及它们的Aldo和皮质醇水平。我们将确定自适应应对是否可以缓冲 Aldo和皮质醇的增加，而适应不良的应对会促进Aldo和皮质醇水平的增加。 此外，我们将确定Aldo和皮质醇水平是否与肾脏风险增加有关 AAS受伤。我们还使用动物模型来确认增加的Aldo和皮质醇会导致肾脏 在高血压的情况下损害。这项研究的结果将是第一个展示基础的结果 种族主义与肾脏疾病之间的病理生理学（ALDO），因此提供了新见解 可能导致对高血压的AA的更精确的治疗，这将阻止肾脏的发展 通常与高血压有关的疾病。