Investigation into Arterial Stiffness and Hypertension

项目概要/摘要 在人类中，大的导管动脉随着年龄的增长和其他病理性变化而失去弹性和扩张。 导致中央动脉硬化和高血压的病症。动脉硬化的患病率 并且高血压随着年龄的增长而增加。目前，对与衰老相关的疾病尚无有效干预措施。 动脉僵硬衰老是心血管疾病的重要危险因素。KDM 6A是一款新... 发现了组蛋白去甲基化酶。该基因的突变会导致严重的胚胎发育缺陷。的 本研究的目的是研究血管平滑肌细胞中KDM 6A是否 血管平滑肌细胞（VSMCs）在动脉顺应性和结构的调节中起作用，并进一步研究 KDM 6A与衰老相关的动脉硬化和高血压有关。这一目标将是 通过追求两个连贯的具体目标，使用几个尖端技术的组合， 接近。两个具体目标是：（1）确定VSMCs中的KDM 6A是否在VSMCs中起作用。 调节动脉顺应性和结构。(2)调查VSMC中的KDM 6A是否参与 与年龄相关的动脉硬化和高血压。所提出的工作具有创新性和重要意义 因为它利用最先进的方法来解决与年龄相关的动脉僵硬度， 人口众多，但仍然知之甚少。结果将揭示新的分子机制 其介导衰老相关的动脉重塑和僵硬以及高血压的发病机制。 该项目的完成可能会为预防和治疗策略提供新的见解， 与年龄相关的动脉硬化和高血压。

Project Summary/Abstract In humans, large conduit arteries lose elasticity and thicken with aging and other pathological conditions leading to central arterial stiffening and hypertension. The prevalence of arterial stiffness and hypertension increases with age. Currently, there is no effective intervention for aging-associated arterial stiffness. Aging is an important risk factor for cardiovascular disease. KDM6A is a recently- discovered histone demethylase. Mutation of this gene causes severe defective embryogenesis. The objective of the proposed research is to investigate if KDM6A in vascular smooth muscle cells (VSMCs) plays a role in the regulation of arterial compliance and structure and further investigate if KDM6A is involved in aging-associated arterial stiffness and hypertension. This objective will be achieved by pursuing two coherent specific aims using a combination of several cutting-edge approaches. The two specific aims are: (1) Determine if KDM6A in VSMCs plays a role in the regulation of arterial compliance and structure. (2) Investigate if KDM6A in VSMCs is involved in the aging-related arterial stiffness and hypertension. The proposed work is innovative and significant because it utilizes state-of-the-art approaches to address aging-related arterial stiffness which affects a large population but remains poorly understood. The results will reveal novel molecular mechanisms that mediate the pathogenesis of aging-associated arterial remodeling and stiffness and hypertension. Completion of this project may provide new insights into preventive and therapeutic strategies for aging-associated arterial stiffness and hypertension.