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

Biomarkers for Muscle Function and Aging in Chronic HIV Infection

慢性 HIV 感染中肌肉功能和衰老的生物标志物

基本信息

批准号：
8951764
负责人：
MONTY A MONTANO
金额：
$ 42.26万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-01 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8951764
关键词：
Address Adult Age Aging Aging-Related Process Agonist Anti-Inflammatory Agents Anti-inflammatory Area Biological Markers Biological Models Biopsy Boston Bromodomain COL1A1 gene COL1A2 gene Cell model Cells Chronic Chronic Disease Coupled Differentiation and Growth Enrollment Fibrin fragment D Fibrosis HIV HIV Infections HIV Seropositivity Health Highly Active Antiretroviral Therapy Homeostasis Human In Vitro Individual Infection Inflammation Inflammatory Interleukin-6 Losartan Lymphoid Tissue Maintenance Measures Modeling Morbidity - disease rate Muscle Muscle Cells Muscle function Musculoskeletal Pathway interactions Patients Peroxisome Proliferator-Activated Receptors Pharmaceutical Preparations Phenotype Physical Function Pilot Projects Population Premature aging syndrome Property Recruitment Activity Reporting Risk Serum Signal Transduction Skeletal Muscle TNF gene TNFRSF1A gene Testing Therapeutic United States United States Food and Drug Administration Viral Load result age related antiretroviral therapy cohort comparison group connective tissue growth factor frailty functional decline functional disability high risk inhibitor/antagonist metropolitan muscle aging muscle regeneration myogenesis myostatin novel protective effect rosiglitazone sex success

项目摘要

DESCRIPTION: In the United States, HIV infection has become a chronic disease with increasing evidence for an accelerated aging phenotype. By 2015, over half of HIV-infected individuals will be 50 years old or older. Notably, chronic HIV infection is associated with persistent inflammation, fibrosis and increased risk for frailty - conditions associated with muscl aging. We propose that persistent inflammation in chronic HIV infection promotes accelerated muscle fibrosis, which is then predicted to accelerate functional impairment, leading to a premature aging phenotype. We suggest that chronic inflammation promotes an imbalance in muscle tissue remodeling resulting in an accelerated, and potentially subclinical muscle fibrosis that is likely to limit physical function in the long term as the HIV population ages. We will recrit a cohort of at risk HIV-infected adults on stable ART and demographically matched uninfected adults to evaluate the following three specific aims: 1. Determine whether inflammation is related to skeletal muscle fibrosis in adults on effective ART. 2. Determine whether skeletal muscle fibrosis is related to physical function. 3. Characterize potential synergy between the fibrotic TGF?1 pathway and inflammatory pathway, and characterize the novel inflammatory inhibitor JQ1, the inflammatory inhibitor Rosiglitazone, and the fibrotic inhibitor Losartan. If fibrosis is confirmed in this study and there is evidence of activated TGF?1 signaling, these patients could be treated with anti-fibrotic agents such as Losartan, a Food and Drug Administration-approved drug with potent anti-fibrotic properties in skeletal muscle.

描述：在美国，艾滋病毒感染已成为一种慢性疾病，越来越多的证据表明艾滋病毒感染会加速衰老表型。到 2015 年，一半以上的艾滋病毒感染者年龄将在 50 岁或以上。值得注意的是，慢性艾滋病毒感染与持续炎症、纤维化和虚弱风险增加有关，虚弱是与肌肉衰老相关的疾病。我们认为，慢性艾滋病毒感染中的持续炎症会加速肌肉纤维化，从而预计会加速功能损伤，导致过早衰老表型。我们认为，慢性炎症会促进肌肉组织重塑的不平衡，从而导致加速的、潜在的亚临床肌肉纤维化，随着艾滋病毒人群的老龄化，从长远来看，这种纤维化可能会限制身体功能。我们将重新招募一组接受稳定 ART 治疗的高危 HIV 感染成年人和人口统计学匹配的未感染成年人，以评估以下三个具体目标： 1. 确定接受有效 ART 治疗的成人中炎症是否与骨骼肌纤维化相关。 2.确定骨骼肌纤维化是否与身体功能有关。 3. 表征纤维化TGF?1通路与炎症通路之间的潜在协同作用，并表征新型炎症抑制剂JQ1、炎症抑制剂罗格列酮和纤维化抑制剂洛沙坦。如果本研究证实纤维化，并且有激活 TGF?1 信号传导的证据，则可以使用抗纤维化药物治疗这些患者，例如氯沙坦，一种美国食品和药物管理局批准的药物，在骨骼肌中具有有效的抗纤维化特性。