Medicina Pulmonar e Respiratória

Angiopoietin-2: A Key to Understanding Sepsis and Its Pulmonary Sequelae?

Abstract

Ji Young Lee and Edmund J. Miller

Sepsis remains a major cause of morbidity and mortality especially in the older individual. In the US alone, sepsis occurs in approximately 750,000 individuals per year and ranks as the tenth leading cause of death. A major complication of sepsis is organ failure, with the lung being one of the first organs to fail. Moreover, sepsis is the most common risk factor for Acute Lung Injury (ALI) and approximately 50% of individuals with sepsis subsequently develop ALI. Despite its importance, the pathophysiology of sepsis remains unclear. Angiopoietin-2 (Ang-2) is a component of pathways involved in endothelial survival and maintenance of a quiescent state of the vascular system. The functional significance of Ang-2 remains to be fully elucidated, but the evidence thus far suggests that it may be key to a better understanding of the vascular dysfunction and associated organ failure that are so devastating in sepsis. However, the assessment of the cellular release of Ang-2 is not without difficulty. In this brief review, we discuss the relevance of Ang-2 to the endothelial dysfunction associated with the severe inflammatory response in sepsis, and why Ang-2 may not be just a biomarker, but may play a critical role in the pathology. In addition, we discuss some of the reasons why particular sepsis models may present confusing data with respect to Ang-2 involvement.