Adiponectin in Acute Lung Injury

描述（由申请人提供）：流行病学证据表明肥胖和急性肺损伤（ALI）之间存在关联，但对介导这种关联的分子机制知之甚少。脂联素是一种脂肪组织来源的激素，在人类和啮齿动物血清中以高浓度存在，并且在小鼠肺中具有充分证明的抗炎和血管保护特性。此外，我们最近证明脂联素可以保护小鼠免受LPS诱导的ALI的发展，并显示较高的循环水平与不同病因的急性呼吸衰竭患者的死亡率增加有关。总之，这些数据支持脂联素在肺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收集的生物标本作为NIH ARDSNet液体和导管治疗试验的一部分，以率先调查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患者中脂联素循环水平较高与更严重的肺损伤表型相关; 2）脂联素血浆水平较高与死亡率增加相关。总之，我们相信这些研究将建立脂联素作为一种新的预后指标在急性肺损伤，并将提供基础，为今后更多的机制研究脂联素在急性肺损伤的作用。

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.