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

• 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
• 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

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，美国人口处于 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翻了一番。重要的是动脉 僵化被认为是可逆的。虽然有许多因素会导致动脉粥样硬化，但我们 提示在PAD患者的动脉中有独特的分子特征与PAD相关。 这些动脉的僵硬和血流状况。我们已经确定了凝血酶反应蛋白-1在 这些条件。在这里，我们将使用体外和体内的方法鉴定和测试这些通路的可修饰性 焊盘状态的模型。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，扰乱这些途径和 改善患者的动脉健康。