Environmental Stress, Genes and Risk of Hypertension

环境压力、基因和高血压风险

• 批准号: 7479054
• 负责人: Frank A Treiber
• 金额: $ 32.14万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7479054
• 关键词: Accounting; Acute; Address; Affect; African American; Age; American; Animals; Antioxidants; Behavioral; Biochemical; Biological; Biological Assay; Biological Markers; Biometry; Blood; Blood Pressure; Blood Vessels; Blood specimen; Body mass index; Budgets; Candidate Disease Gene; Cardiovascular Diseases; Cardiovascular system; Carotid Atherosclerotic Disease; Childhood; Chronic; Chronic stress; Comorbidity; Corticotropin-Releasing Hormone Receptors; Dahl Hypertensive Rats; Development; Discrimination; Disease; Early identification; Economics; Endothelium; Environment; Epidemic; Essential Hypertension; Etiology; European; Evaluation; Excretory function; Exhibits; Exposure to; Family; Fasting; Figs - dietary; Forehead; Freezing; Functional disorder; Future; Genes; Genetic; Genetic Predisposition to Disease; Genotype; Glucocorticoid Receptor; Glucose; Health; High Blood Pressure; High Density Lipoprotein Cholesterol; Homeostasis; Homologous Gene; Human; Hydrocortisone; Hypertension; Hypertriglyceridemia; Hypothalamic structure; Individual; Individual Differences; Insulin; Insulin Resistance; Interview; Invasive; Kidney; Laboratories; Left Ventricular Mass; Life; Light; Link; Lipids; Longitudinal Studies; Manuscripts; Measurement; Measures; Mediating; Metabolic; Modeling; Morbidity - disease rate; Nervous System Physiology; Norepinephrine; Obesity; Oxidants; Oxidative Stress; Oxidative Stress Pathway; Pathway interactions; Patients; Pattern; Pharmacogenetics; Pharmacologic Substance; Physiologic pulse; Physiological; Pituitary Gland; Plasma; Play; Preparation; Prevention approach; Principal Investigator; Process; Psychosocial Stress; Pulse taking; Reactive Oxygen Species; Receptor Gene; Regulation; Renin-Angiotensin System; Research; Research Design; Rest; Risk; Role; Salivary; Sampling; Secondary Prevention; Services; Slide; Sodium; Spottings; Stress; Superoxide Dismutase; Sympathetic Nervous System; System; Technology; Testing; Thick; Time; United States; Urine; Variant; Vascular remodeling; Ventricular Remodeling; Video Games; Visit; Vitamins; Work; Youth; abuse neglect; acute stress; arterial stiffness; base; biobehavior; biological adaptation to stress; blood pressure regulation; cohort; data management; design; extracellular; follow-up; gene environment interaction; hemodynamics; human CYBA protein; human study; improved; indexing; intima media; lifestyle intervention; mimetics; pediatric trauma; post gamma-globulins; posters; pre-clinical; programs; receptor; response; social; stressor; urinary

The objective of Project 2 is to ascertain how chronic environmental stress in combination with unfavorable genotypes via 2 new mechanistic pathways (hypothalamic-pituitary-adrenocortical [HPA] axis and oxidative stress) affects BP reactivity to acute stress and development of preclinical cardiovascular disease (CVD). The Project will study a cohort of 300 African Americans and 307 European Americans (mean age will be 25.5 yrs) who have been evaluated 14 times over a 17-year period. The continued follow-up of this cohort will allow us to examine the cumulative effects of environmental stress, genotypes and their interaction on the time course of the development of preclinical measures of CVD over a period of 22 years. Subjects will have hemodynamic measures and indices of HPA axis and oxidative stress assessed prior to and immediately following three acute laboratory challenges, as well as in the naturalistic field setting. Subjects will also have measures of preclinical CVD evaluated. Two key genes in each of the HPA and oxidative stress pathways will be assessed by a gene-wide approach with all variants within a candidate gene considered jointly. In context of the recent evidence suggesting that activation of HPA axis and oxidative stress play an important role in obesity related EH, we hypothesize that obesity will exacerbate the activation of these two pathways which are elevated by chronic environmental stress. Specific aims of Project 2 are to test the hypotheses that individuals from chronically stressful environments and/or with unfavorable genotypes will exhibit greater increases over time in HPA axis and oxidative stress response to acute stressors and chronic stress (i.e., natural environment assessment) and measures of preclinical CVD. Possible moderating influences of obesity will also be examined. We will also test the hypotheses that individuals with higher levels (when originally measured) and/or greater increases over time in HPA and oxidative stress responses to acute stress will exhibit higher levels of BP reactivity and measures of preclinical CVD. The long term objective of Project 2 is to improve the understanding of the way stress contributes to the development of EH. Findings will contribute to development of behavioral pharmacogenetic therapies which will include lifestyle interventions and pharmaceutical therapies in which the role of stress is taken into account. These efforts will result in more efficacious and personalized primary and secondary prevention approaches of EH and its co-morbidities.

项目2的目标是确定慢性环境压力如何与不利的 通过两条新的机制途径(下丘脑-垂体-肾上腺皮质[HPA]轴和氧化作用)实现的基因分型 应激)影响血压对急性应激的反应性和临床前心血管疾病(CVD)的发展。 该项目将研究300名非洲裔美国人和307名欧洲裔美国人(平均年龄为 25.5年)，他们在17年的时间里接受了14次评估。这一队列的持续后续行动 将使我们能够检验环境压力、基因类型及其相互作用对 22年来心血管疾病临床前措施发展的时间进程。研究对象将 在此之前和之前评估HPA轴和氧化应激的血流动力学测量和指数 紧接在三个实验室的尖锐挑战之后，以及在自然主义的野外环境中。科目 还将对临床前心血管疾病的测量进行评估。HPA和氧化各有两个关键基因 应激途径将通过一个候选基因内的所有变异的全基因方法进行评估。 共同考虑。最近的证据表明，HPA轴的激活和氧化 压力在肥胖相关的高血压中起着重要的作用，我们假设肥胖会加剧 激活这两条因慢性环境应激而升高的通路。的具体目标 项目2是测试来自长期压力环境和/或有 随着时间的推移，不利的基因型会在HPA轴和氧化应激反应中表现出更大的增加 急性应激源和慢性应激(即自然环境评估)和临床前心血管疾病的措施。 此外，还将研究肥胖可能产生的缓解影响。我们还将检验假设 HPA和HPA水平较高(最初测量时)和/或随时间增加较多的个人 对急性应激的氧化应激反应将表现出更高水平的BP反应性和措施 临床前脑血管病。 项目2的长期目标是提高对压力对心理健康的影响的理解。 高血压病的发展。这些发现将有助于开发行为药物遗传疗法， 将包括生活方式干预和药物治疗，其中压力的作用被纳入 帐号。这些努力将产生更加有效和个性化的一级和二级预防。 高血压病及其并发症的治疗方法。