Characterization of Apolipoprotein A-I Pathways in Idiopathic Pulmonary Fibrosis

特发性肺纤维化(IPF)是一种慢性进行性疾病，主要发生在55岁至75岁的老年人中，确诊后中位生存期约为3年。目前，还没有针对IPF患者的有效治疗方法。已发现IPF患者肺中载脂蛋白A-I(apoA-I)水平降低，而在小鼠模型中，给药人apoA-I已被证明可减少博莱霉素诱导的胶原沉积。在这里，我们想评估载脂蛋白A-I通路是否改变了IPF患者的肺细胞生物学。这是一项标本获取、临床表型和基因分型方案，将评估全脂载脂蛋白A-I和载脂蛋白A-I模拟肽是否能够减轻IPF的关键致病表现，如肺成纤维细胞的增殖和细胞外基质的产生，这可能为未来apoA-I治疗IPF的人类临床试验提供证据。此外，识别新的载脂蛋白A-I应答基因和途径在特发性肺纤维化中介导成纤维细胞的增殖可能为深入了解疾病的发病机制和确定新的治疗靶点提供帮助。最后，如果诱导多能干细胞(IPS)可以成功地模拟肺细胞对apoA-I治疗的反应性，那么这种方法可能会被扩展，目标是提供个性化的药物分析，在未来指导为个别患者选择最有效的治疗方法。

Idiopathic Pulmonary Fibrosis (IPF) is a chronic progressive disease that occurs primarily in older individuals, 55 to 75 years of age, with a median survival of approximately 3 years from time of diagnosis. At present, there are no effective treatments for patients with IPF. Levels of apolipoprotein A-I (apoA-I) have been found to be reduced in the lungs of patients with IPF, while administration of human apoA-I has been shown to reduce bleomycin-induced collagen deposition in a murine model. Here, we would like to assess whether apoA-I pathways modify lung cell biology in patients with IPF. This is a specimen procurement, clinical phenotyping and genotyping protocol that will assess whether holo-apoA-I and apolipoprotein A-I mimetic peptides, can attenuate key pathogenic manifestations of IPF, such as proliferation and extracellular matrix generation by pulmonary fibroblasts, which may serve as evidence to support future human clinical trials of apoA-I for the treatment of IPF. Furthermore, the identification of new apoA-I responsive genes and pathways that mediate fibroblast proliferation in IPF may provide insights into disease pathogenesis and identify new therapeutic targets. Lastly, if induced pluripotent stem (iPS) cells can be successfully shown to model responsiveness of lung cells to apoA-I therapy, then this approach may be expanded with the goal of providing a personalized medicine analysis that could in the future guide selection of the most effective therapy for individual patients.