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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：
10226978
负责人：
LUKE Packard BREWSTER
金额：
$ 73.69万
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/10226978
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 conditional knockout 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.

摘要由于老龄化和心血管疾病患者寿命的延长，美国人口在患外周动脉疾病的风险不断增加。外周动脉疾病患者有动脉硬化和外周动脉疾病使患者的心血管死亡率增加一倍。重要动脉硬化被认为是可逆的。虽然有许多因素导致动脉粥样硬化，我们我认为PAD患者的动脉中存在独特的分子特征，这些动脉的硬度和流动状况。我们已经确定了血小板反应蛋白-1在了以下条件在这里，我们将确定和测试这些途径的可修改性，使用在体外和体内 PAD条件的模型。为了测试这项工作的翻译，人体组织将被用来测试关键调查结果。积极的结果将有助于制定有针对性的战略，破坏这些途径，改善患者的动脉健康。