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

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。

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.