Investigation into Arterial Stiffness and Hypertension

动脉僵硬和高血压的调查

基本信息

批准号：
10251335
负责人：
Zhongjie Sun
金额：
$ 55.93万
依托单位：
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10251335
关键词：
Address Affect Age Aging Animals Arteries Blood Vessels Cardiovascular Diseases Cardiovascular system Clinical Research Collagen Data Development Elastases Elasticity Elastin Embryonic Development Environment Etiology Focal Adhesion Kinase 1 Gene Expression Gene Mutation Genes Genetic Transcription High Prevalence Histones Human Hypertension Investigation Longevity Lysine Maintenance Mediating Molecular Mus Mutation Pathogenesis Pathologic Pathway interactions Phase Phenotype Play Population Population Study Positioning Attribute Prevalence Preventive Regulation Research Role Smooth Muscle Myocytes Societies Structure Systemic hypertension Testing Therapeutic Therapeutic Intervention Up-Regulation Vascular Smooth Muscle Work acute myeloid leukemia 1 protein aged arterial remodeling arterial stiffness cardiovascular risk factor effective intervention histone demethylase in vivo innovation insight mortality novel overexpression preventive intervention protein expression scleraxis targeted treatment

项目摘要

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.

项目概要/摘要在人类中，大导管动脉会随着衰老和其他病理原因失去弹性并增厚导致中央动脉硬化和高血压的疾病。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，对于衰老相关的问题还没有有效的干预措施动脉僵硬度。衰老是心血管疾病的重要危险因素。 KDM6A 是最近- 发现了组蛋白去甲基化酶。该基因的突变会导致胚胎发生严重缺陷。这拟议研究的目的是调查血管平滑肌细胞中的 KDM6A 是否存在（VSMC）在动脉顺应性和结构的调节中发挥作用，并进一步研究是否 KDM6A 与衰老相关的动脉硬化和高血压有关。这一目标将是通过结合多种前沿技术追求两个连贯的具体目标来实现接近。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) 考察VSMCs中的KDM6A是否参与了与衰老相关的动脉硬化和高血压。拟议的工作具有创新性和意义因为它利用最先进的方法来解决与衰老相关的动脉僵硬度，这会影响人口众多，但人们对其了解甚少。结果将揭示新的分子机制介导与衰老相关的动脉重塑、僵硬和高血压的发病机制。该项目的完成可能会为以下疾病的预防和治疗策略提供新的见解：与衰老相关的动脉硬化和高血压。