Sepsis and the broken endothelium 英文参考文献.docVIP

Shapiro and Aird Critical Care 2011,15:135 /content/15/2/135 COMMENTARY Sepsis and the broken endothelium Nathan I Shapiro* and William C Aird 1 2 See related research by Yang et al., /content/15/1/R11 sVEGFR ese studies have shown that VEGF Abstract exacerbates sepsis and mediates morbidity and mortality, while it is thought that circulating sVEGFR-1 binds and neutralizes the adverse/pro-in? ammatory e? ects of The study by Yang and colleagues examined 81 patients with septic shock due to pneumonia, along with 20 patients with pneumonia without organ dysfunction. Their major ?ndings were that circulating levels of soluble vascular endothelial cell growth factor receptor-1 (sVEGFR-1) and urokinase-type plasminogen activator (uPA) were associated with organ dysfunction and mortality, whereas vascular endothelial cell growth factor (VEGF) levels had no such predictive power. Yang and colleagues are to be complimented for a well-conducted study of a reasonably (and helpfully!) homogeneous population of patients with sepsis that carefully and comprehensively analyzed the relationship between sVEGFR-1, uPA, VEGF and clinical outcome. The study serves not only to provide evidence in support of new diagnostic biomarker targets in sepsis, but also to augment the growing evidence of an important role of the endothelium in sepsis in general, and the VEGF signaling axis in particular. VEGF is hypothesis is supported by the observation that supratherapeutic levels of sVEGFR-1 in murine models of sepsis deplete the blood of free VEGF and protect against morbidity and mortality. If sVEGFR-1 is protective, then why are elevated circulating levels of sVEGFR-1 associated with worse clinical outcome in sep e apparent dichotomy may be explained by one or more of the following hypotheses: 1, sVEGFR-1 levels simply re? ect the vigor of the anti- in? am