Molecular Mechanisms of Flow-dependent Arterial Remodeling in Peripheral Arterial Disease

外周动脉疾病中血流依赖性动脉重塑的分子机制

基本信息

批准号：
9751378
负责人：
LUKE Packard BREWSTER
金额：
$ 77.7万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9751378
关键词：
Affect Aging Animal Model Animals Arterial Fatty Streak Arteries Atherosclerosis Biology Biomechanics Blood Vessels Blood flow Cardiovascular Diseases Cardiovascular system Collagen Gene Control Groups Critical Pathways Cultured Cells Data Deposition Disease Disease Progression Disease model Elastin Endothelial Cells Environment FBLN5 gene Female Fibrosis Functional disorder Gene Expression Goals Health High Fat Diet Histology Human In Vitro Infection Knock-out Knockout Mice Lead Longevity Mechanics Mediating Mediator of activation protein Medical Molecular Molecular Profiling Molecular Target Mus Natural History Pathologic Pathway interactions Patients Peptides Peripheral arterial disease Population Research Risk Role Severities Signal Pathway Signal Transduction Surgical Flaps Tamoxifen Testing Therapeutic Thrombospondin 1 Time Tissues Transforming Growth Factor beta Translating Translations Up-Regulation Work age related aged arterial remodeling arterial stiffness clinically relevant connective tissue growth factor human female human tissue improved in vitro Assay in vitro testing in vivo in vivo Model in vivo evaluation knockout animal male mortality multidisciplinary novel premature response shear stress

项目摘要

Abstract Due to both aging and the improved longevity of patients with cardiovascular disease, the US population is at an ever-increasing risk of developing peripheral arterial disease. Patients with peripheral arterial disease have stiffened arteries, and peripheral arterial disease doubles patients' cardiovascular mortality. Importantly arterial stiffening is thought to be reversible. While there are a number of factors that lead to atherosclerosis, we propose that there are unique molecular signatures in arteries of patients with PAD that are related to the stiffness and flow conditions of these arteries. We have identified an important role for thrombospondin-1 in these conditions. Here we will identify and test the modifiability of these pathways using in vitro and in vivo models of PAD conditions. In order to test translation of this work, human tissue will be used to test critical findings. Positive results will be useful in developing targeted strategies that disrupt these pathways and improve arterial health in our patients.

抽象的由于衰老和心血管疾病患者的寿命改善，美国人口处于发生周围动脉疾病的风险不断增加。周围动脉疾病的患者患有僵硬的动脉和周围动脉疾病会使患者的心血管死亡率增加一倍。重要的是动脉僵硬被认为是可逆的。虽然有许多因素导致动脉粥样硬化，但我们提出与PAD患者的动脉中有独特的分子特征这些动脉的刚度和流动条件。我们已经确定了血小板传播1在这些条件。在这里，我们将使用体外和体内识别并测试这些途径的可修改性垫条件的模型。为了测试这项工作的翻译，人体组织将用于测试关键发现。积极的结果将有助于制定破坏这些途径的目标策略和改善我们患者的动脉健康。