Role of ARF6 in atherosclerotic burden and severity

大约9200万美国成年人至少患有一种心血管疾病(CVD)，每年 心血管疾病和中风的直接医疗费用估计超过3150亿美元。在美国老兵中，CVD是 根据退伍军人事务部的说法，住院的主要原因和残疾的主要原因 研究和开发，约80%的退伍军人目前有两个以上的心血管疾病危险因素。动脉粥样硬化 疾病是心血管疾病的一种主要形式。其严重性和相关的发病率/死亡率是 不仅取决于斑块的整体负荷，还取决于斑块的稳定性或易损性。因此，一个 更好地了解细胞生长和稳定的潜在机制和细胞类型 斑块是提供新疗法的关键。ADP核糖化因子6(Arf6)是RAS家族中的一员。 调节细胞增殖和运动以及膜运输的小GTP酶。ARF6参与了 与动脉粥样硬化相关的炎症和动脉功能，包括免疫细胞黏附/激活， 内皮细胞通透性与血管生成。然而，arf6在动脉粥样硬化中的作用尚未得到证实。 描述。我们的目的是阐明调节全身和组织特异性Arf6对斑块的影响。 负担、成分和稳定性，以及探索药理Arf6抑制作为抗动脉粥样硬化 心理治疗。

Approximately 92 million US adults have at least one form of cardiovascular disease (CVD), with the annual direct health care cost of CVD and stroke estimated to exceed $315 billion. Among US Veteran’s, CVD is the leading cause of hospitalizations and a major cause of disability and according to the VA Health Services Research and Development, ~80% of Veteran’s present with more than two CVD risk factors. Atherosclerotic diseases are a predominate form of CVD. The severity and associated morbidity/mortality of which is determined not only by overall plaque burden, but also by the stability, or vulnerability, of plaques. Thus, a better understanding of the underlying mechanisms and cell types involved in the growth and stability of plaques is critical to inform novel therapies. ADP ribosylation factor 6 (Arf6) is a member of the RAS family of small GTPases that regulates cell proliferation and motility as well as membrane trafficking. Arf6 is involved in inflammatory and arterial functions related to atherosclerosis, including immune cell adhesion/activation, endothelial cell permeability and angiogenesis. However, a role for Arf6 in atherosclerosis has not been described. We aim to elucidate the effects of modulating whole body and tissue-specific Arf6 on plaque burden, composition and stability, as well as explore pharmacological Arf6 inhibition as an anti-atherosclerotic therapy.