权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Role of Adiponectin in Reversal of Age-related Vascular Dysfunction

脂联素在逆转年龄相关血管功能障碍中的作用

基本信息

批准号：
10566303
负责人：
JUDY M DELP
金额：
$ 52.09万
依托单位：
FLORIDA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-02-15 至 2026-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10566303
关键词：
Acute Adjuvant Aerobic Exercise Age Aging Agonist Arteries Biomedical Research Blood Blood Vessels Blood flow Cardiovascular Diseases Cardiovascular system Ceramides Coronary Development Disease Elderly Elements Endothelium Exercise Functional disorder Goals Impairment Inflammation Knock-out Longevity Microvascular Dysfunction Mus Myocardium Organ Phenotype Prevention Proteins Rattus Reporting Research Priority Resistance Risk Factors Role Signal Pathway Signal Transduction Skeletal Muscle Smooth Muscle Sphingosine Structure Testing Training Vascular Diseases Vascular Smooth Muscle Vascular remodeling Vasomotor Work adiponectin age related aged antagonist arterial remodeling blood pressure regulation cardiac vasculature cardiovascular effects endothelial dysfunction exercise training gain of function improved loss of function middle age mimetics novel pharmacologic promote resilience protective effect receptor resilience response sedentary senescence therapeutic target young adult

项目摘要

Aging is a primary risk factor for development of cardiovascular dysfunction and disease. The hallmarks of vascular aging are endothelial dysfunction, development of a synthetic, atherosclerotic phenotype in smooth muscle, and arterial inflammation and stiffening. We have shown that aerobic exercise training can mitigate or reverse age-related vascular dysfunction and adverse arterial remodeling; however, the cellular signals that contribute to the ability of exercise training to promote macro- and microvascular resiliency remain unidentified. Similarly, the mechanisms whereby exercise training reverses age- related vascular dysfunction remain unknown. Reduced circulating adiponectin has been associated with the adverse vascular changes that occur with advancing age; however, a role for adiponectin in age- related vascular dysfunction has not been demonstrated. We have reported that circulating adiponectin levels increase in response to late-life exercise training; however, a direct role for adiponectin signaling in reversal of age-related vascular dysfunction by exercise training has not been demonstrated. We propose to test a central hypothesis that 1) loss of adiponectin is a critical contributor to age- related vascular dysfunction and adverse arterial remodeling, and 2) adiponectin contributes to the ability of exercise training to promote vascular resiliency and reverse age-related vascular dysfunction and age-related adverse vascular remodeling. We propose to study sedentary and exercise trained mice, across the murine lifespan, to determine 1) the impact of loss- and gain-of-function of adiponectin on ceramide/sphingosine signaling in the endothelium of the microvasculature of the heart and skeletal muscle, 2) the impact of loss- and gain-of-function of adiponectin on development of a senescence-associated synthetic phenotype in vascular smooth muscle and contractile dysfunction the microvasculature of the heart and skeletal muscle, and 3) the impact of loss- and gain-of-function of adiponectin on remodeling of large arteries. Results from the proposed work will increase our understanding of the role of adiponectin in age-related vascular dysfunction and exercise training-induced reversal of age-related vascular dysfunction. A top biomedical research priority is to identify strategies which promote vascular resiliency with advancing age or which reverse age-related vascular dysfunction. The proposed work could identify 1) components of the adiponectin signaling pathway that could be targeted for prevention of age-related vascular dysfunction, and 2) novel exercise mimetics that could be employed for 1) promotion of vascular resiliency across the lifespan, and/or 2) reversal of age-related vascular dysfunction.