AGING AND HYPERTENSION--GENDER, GENES AND RISK

描述：(改编自申请人的摘要)。此应用程序用于 指导临床科学家发展奖。申请人声明： 心血管风险中的性别二型性随着年龄的增长而演变， 女性患高血压和心脏病的几率明显减少 尽管这种差异随着年龄的增长而消失， 尤其是在黑人中。这项提案中的研究计划旨在进行 初步证据表明，年龄、性别和种族起着关键作用 在改变遗传风险的最终表达方面的作用。特别是， 初步数据显示，女性受到保护，不会表现出 高血压的常见中间表型，以异常为标志 对血管紧张素II的反应性。在许多被提出的基因中 导致人类高血压，这是为数不多的与高血压相关的疾病之一 有记载的是血管紧张素原(AGT)的编码，它是 肾素-血管紧张素系统--然而，只有在 男性。目前的提议旨在检验这样一种假设，即最终 AGT基因的表达受年龄、性别和 荷尔蒙状态。它将测试女性激素替代疗法是否 (HRT)可以提供与内源性类固醇激素相同的保护作用； 种族是否影响AGT基因与高血压病患者的关系 血管反应性的表型；以及营养因素、 最终涉及到肥胖，这是有贡献的。 由于预期获奖，申请者的计划是继续临床研究 高血压病中肾、肾上腺的应用技巧与认识 生理学对衰老过程的影响。由HER控制的生理学研究 将在布里格姆和女子医院的临床研究中心进行 医院。此外，她将得到刘易斯·利普西茨博士的指导，他是 在老年人群的心血管功能和疾病方面有丰富经验。 申请者声明的目标是为她自己建立一个独立的 研究心血管、肾脏和肾上腺的研究职业道路 功能与老年高血压发病机制的关系。

DESCRIPTION: (Adapted from applicant's abstract). This application is for a Mentored Clinical Scientist Development Award. The applicant states that that sexual dimorphisms in cardiovascular risk evolve with increasing age, and that women experience significantly less hypertension and heart disease than do men -- though this difference disappears with increasing age, especially among Blacks. The research plan in this proposal aims to pursue preliminary evidence which suggests that age, gender and race play a key role in modifying the ultimate expression of genetic risk. In particular, preliminary data reveal that females are protected against expression of a common intermediate phenotype of essential hypertension, marked by abnormal responsiveness to angiotensin II. And among the many genes proposed to cause human hypertension, one of the very few for which linkage has been documented is that coding for angiotensinogen (AGT), a key element of the renin-angiotensin system - yet linkage has been convincingly shown only in males. The present proposal aims to test the hypothesis that the ultimate expression of the AGT gene is strongly influenced by age, gender, and hormonal status. It will test whether female hormone replacement therapy (HRT) can confer the same protection as do endogenous sex steroid hormones; whether race influences the relationship between AGT genotype and the phenotype of AngII responsiveness; and whether nutritional factors, ultimately involving obesity, contribute. With anticipated award the applicant's plan is to continue clinical research in hypertension, applying techniques and understanding of renal and adrenal physiology to the process of aging. Controlled physiologic studies by her will be performed on the Clinical Research Center of the Brigham and Women's Hospital. As well, she will be mentored by Dr. Lewis Lipsitz who is experienced in cardiovascular function and disease in the aging populations. The applicant's stated goal is to establish for herself an independent research career path for studying cardiovascular, renal, and adrenal function in relation to the pathogenesis of hypertension in the elderly.