Adiponectin in Acute Lung Injury

描述（由申请人提供）：流行病学证据表明肥胖与急性肺损伤（ALI）之间存在关联，但介导这种关联的分子机制尚不清楚。脂联素是一种来源于脂肪组织的激素，在人类和啮齿类动物血清中存在高浓度，在小鼠肺中具有良好的抗炎和血管保护作用。此外，我们最近证明了脂联素可以防止lps诱导的小鼠急性呼吸衰竭的发生，并表明在多种病因的急性呼吸衰竭患者中，较高的循环水平与死亡率增加有关。总之，这些数据支持了脂联素在肺内稳态和疾病中起重要作用的观点。在这个项目中，我们将利用现有的临床数据和作为NIH ARDSNet液体和导管治疗试验的一部分收集的生物标本，以率先研究脂联素在急性肺损伤中的作用。本项目将研究以下假设：1)ALI患者较高的循环脂联素水平与更严重的肺损伤表型有关；2)较高的血浆脂联素水平与死亡率增加有关。总的来说，我们相信这些研究将确立脂联素作为ALI的一种新的预后标志物，并将为未来更多关于脂联素在ALI中的作用的机制研究提供基础。

DESCRIPTION (provided by applicant): Epidemiological evidence indicates an association between obesity and acute lung injury (ALI), but the molecular mechanisms mediating this association are poorly understood. Adiponectin is an adipose tissue-derived hormone that is present in high concentration in serum of humans and rodents and has well-documented anti-inflammatory and vascular protective properties in murine lung. Moreover, we recently demonstrated adiponectin to protect against development of LPS-induced ALI in mice and showed higher circulating levels are linked to increased mortality in patients with established acute respiratory failure of diverse etiologies. Together, these data support the notion that adiponectin plays an important role in lung homeostasis and disease. In this program, we will leverage existing clinical data and bio-specimens collected as part of the NIH ARDSNet Fluid and Catheter Treatment Trial in order to spearhead investigation into role of adiponectin in acute lung injury. This project will investigate the hypotheses that: 1) higher circulating levels f adiponectin in patients with ALI are linked to a more severe lung injury phenotype; and 2) higher plasma levels of adiponectin are associated with increased mortality. Overall, we believe these studies will establish adiponectin as a novel prognostic marker in ALI and will provide the foundation for future more mechanistic studies into the role of adiponectin in ALI.