Abstract:
RATIONALE:The acute respiratory distress syndrome is a significant cause of morbidity and mortality in critically ill patients. Angiopoietin-1 (Ang-1), a ligand for the endothelial Tie2 receptor, is an endothelial survival and vascular stabilization factor that reduces endothelial permeability and inhibits leukocyte-endothelium interactions. OBJECTIVES:We hypothesized that Ang-1 counteracts vascular inflammation and pulmonary vascular leak in experimental acute lung injury. METHODS:We used cell-based gene therapy in a rat model of ALI. Transgenic mice overexpressing Ang-1 or deficient in the Tie2 receptor were also studied to better elucidate the mechanisms of protection. MEASUREMENTS AND MAIN RESULTS:The present report provides data that support a strong protective role for the Ang-1/Tie2 system in two experimental models of LPS-induced acute lung injury. In a rat model, cell-based Ang-1 gene transfer improved morphological, biochemical, and molecular indices of lung injury and inflammation. These findings were confirmed in a gain-of-function conditional, targeted transgenic mouse model, in which Ang-1 reduced endothelial cell activation and the expression of adhesion molecules, associated with a marked improvement in airspace inflammation and intraalveolar septal thickening. Moreover, heterozygous Tie2-deficient mice demonstrated enhanced evidence of lung injury and increased early mortality. CONCLUSIONS:These results support a critical role for the Ang-1/Tie2 axis in modulating the pulmonary vascular response to lung injury and suggest that Ang-1 therapy may represent a potential new strategy for the treatment and/or prevention of acute respiratory distress syndrome in critically ill patients.
journal_name
Am J Respir Crit Care Medauthors
McCarter SD,Mei SH,Lai PF,Zhang QW,Parker CH,Suen RS,Hood RD,Zhao YD,Deng Y,Han RN,Dumont DJ,Stewart DJdoi
10.1164/rccm.200609-1370OCsubject
Has Abstractpub_date
2007-05-15 00:00:00pages
1014-26issue
10eissn
1073-449Xissn
1535-4970pii
200609-1370OCjournal_volume
175pub_type
杂志文章abstract::We investigated the relationship between annual change in pulmonary function and changes in respiratory symptoms among male grain elevator workers who participated in a health surveillance program mandated by Labour Canada. The surveillance was conducted every 3 yr starting from the period 1978 to 1981. The 1,211 work...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.2.8564120
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abstract::Inhaled nitric oxide (NO) improves systemic oxygenation (PaO2/FIO2) in adult patients with acute respiratory distress syndrome (ARDS). However, individual response varies, and previous trials demonstrated no outcome benefit. This prospective, randomized study in 40 ARDS patients analyzed dose-response (DR) characteris...
journal_title:American journal of respiratory and critical care medicine
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journal_title:American journal of respiratory and critical care medicine
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