Environmental Stress, Genes and Risk of Hypertension

项目2的目标是确定长期环境压力如何与不利的环境压力相结合， 基因型通过2个新的机制途径（下丘脑-垂体-肾上腺皮质[HPA]轴和氧化 应激）影响BP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名欧洲裔美国人的队列（平均年龄为20岁）。 25.5在17年的时间里接受了14次评估。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对 在22年的时间内开发CVD的临床前测量的时间过程。受试者将 在术前和术后评估血液动力学指标和HPA轴指数以及氧化应激， 紧接着三个急性实验室的挑战，以及在自然的领域设置。科目 还将评估临床前CVD的指标。两个关键基因在每个HPA和氧化 应激途径将通过候选基因内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轴的激活和氧化应激可能是一个重要的因素。 应激在肥胖相关EH中起重要作用，我们推测肥胖会加重 这两种途径的激活是由慢性环境应激引起的。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人的假设 不利的基因型将表现出HPA轴和氧化应激反应随时间的更大增加， 急性应激源和慢性应激（即，自然环境评估）和临床前CVD的测量。 肥胖可能的调节影响也将被检查。我们还将检验以下假设： HPA水平较高（最初测量时）和/或随时间增加较大的个体， 对急性应激的氧化应激反应将表现出更高水平的BP反应性， 临床前CVD。 项目2的长期目标是提高对压力如何促进 发展EH。研究结果将有助于发展行为药物遗传学疗法， 将包括生活方式干预和药物治疗，其中考虑到压力的作用， 帐户.这些努力将导致更有效和个性化的初级和二级预防 EH及其合并症的治疗方法。

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.