Environmental Stress, Genes and Risk of Hypertension

环境压力、基因和高血压风险

基本信息

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
项目类别：
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

项目摘要

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 的目标是确定长期环境压力与不利因素的结合如何影响通过 2 条新机制途径（下丘脑-垂体-肾上腺皮质 [HPA] 轴和氧化压力）影响血压对急性压力的反应以及临床前心血管疾病（CVD）的发展。该项目将研究 300 名非洲裔美国人和 307 名欧洲裔美国人的队列（平均年龄为 25.5 岁），在 17 年期间接受了 14 次评估。对该队列的持续随访将使我们能够研究环境压力、基因型及其相互作用的累积影响 22 年期间 CVD 临床前措施开发的时间进程。受试者将在之前和之前评估了血流动力学指标以及 HPA 轴和氧化应激指数紧接着三个严峻的实验室挑战以及自然主义现场环境。科目还将对临床前 CVD 指标进行评估。 HPA 和氧化各有两个关键基因应激途径将通过全基因范围的方法对候选基因内的所有变异进行评估共同考虑。最近的证据表明 HPA 轴的激活和氧化压力在肥胖相关的 EH 中起着重要作用，我们假设肥胖会加剧 EH 这两条途径的激活会因慢性环境压力而升高。具体目标项目 2 旨在测试来自长期压力环境和/或患有慢性压力环境的个体的假设不利的基因型将随着时间的推移，HPA 轴和氧化应激反应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）以及临床前 CVD 的测量。还将研究肥胖可能的调节影响。我们还将检验以下假设： HPA 水平较高（最初测量时）和/或随时间推移增加幅度较大的个体，对急性应激的氧化应激反应将表现出更高水平的血压反应性和测量临床前CVD。项目 2 的长期目标是提高对压力如何影响健康的理解。 EH的发展。研究结果将有助于行为药物遗传学疗法的发展将包括生活方式干预和药物治疗，其中考虑了压力的作用帐户。这些努力将带来更有效和个性化的一级和二级预防 EH 及其合并症的治疗方法。