AGING AND HYPERTENSION--GENDER, GENES AND RISK

描述：（改编自申请人摘要）。 此应用程序用于 临床科学家发展指导奖。 申请人指出， 心血管疾病风险中的两性异形随着年龄的增长而发展， 女性患高血压和心脏病的几率也大大降低 比男性更有活力--尽管这种差异随着年龄的增长而消失， 尤其是黑人。 本提案中的研究计划旨在 初步证据表明，年龄、性别和种族是 在改变遗传风险的最终表达中的作用。 特别是， 初步数据显示，女性受到保护，不表达一种 原发性高血压的常见中间型，以异常 对血管紧张素II的反应性。 在众多基因中， 导致人类高血压，其中一个极少数的联系已经 血管紧张素原（AGT）的编码是血管紧张素原（AGT）的关键因素， 肾素-血管紧张素系统-然而，只有在 男性。 本提案旨在检验以下假设： 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; 种族是否影响AGT基因型与 AngII反应性的表型;以及是否营养因素， 最终导致肥胖的原因。 申请人计划继续进行临床研究， 在高血压中，应用技术和对肾和肾上腺的理解 生理学对衰老过程的影响 她的对照生理学研究 将在布里格姆和妇女的临床研究中心进行 医院 同时，她将由刘易斯利普西茨博士指导， 在老年人群的心血管功能和疾病方面经验丰富。 申请人声明的目标是为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 与老年高血压发病机制有关。

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.