Investigation into Arterial Stiffness and Hypertension

项目摘要/摘要 在人类中，大的导管动脉随着年龄的增长和其他病理变化而失去弹性和增厚。 导致中央动脉僵硬和高血压的情况。动脉僵硬的患病率 高血压随着年龄的增长而增加。目前，还没有对衰老相关的有效干预措施 动脉僵硬。衰老是心血管疾病的重要危险因素。KDM6A是一款最近推出的- 发现了组蛋白去甲基酶。该基因的突变会导致严重的胚胎发育缺陷。这个 该研究的目的是研究KDM6A是否存在于血管平滑肌细胞中 (VSMCs)在调节动脉顺应性和结构中发挥作用，并进一步研究是否 KDM6A与衰老相关的动脉僵硬和高血压有关。这一目标将是 通过使用几个尖端技术的组合来实现两个连贯的特定目标 接近了。两个具体目标是：(1)确定VSMC中的KDM6A是否在 动脉顺应性和结构的调节。(2)调查VSMCs中的KDM6A是否参与了 与年龄相关的动脉僵硬和高血压。建议的工作具有创新性和重要意义。 因为它使用最先进的方法来解决与衰老相关的动脉僵硬问题，这会影响 人口众多，但人们对此仍知之甚少。研究结果将揭示新的分子机制。 它们参与了衰老相关动脉重构、僵硬和高血压的发病机制。 该项目的完成可能为预防和治疗艾滋病的策略提供新的见解 增龄相关的动脉僵硬和高血压。

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.