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Angiopoietin‐1 attenuates microvascular hyperpermeability and decreases Smac levels following hemorrhagic shock
Author(s) -
Childs Ed,
Tharakan Binu,
Hunter Felicia
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1384
Hemorrhagic shock (HS) results in the disruption of the endothelial cell barrier followed by an increase in permeability. Recent studies have shown that Angiopoietin (Ang‐1) attenuates endothelial cell permeability. In addition, Ang‐1 has also been shown to decrease the proapoptotic factor Smac. The main objectives of this study were to determine if Ang‐1 is effective in maintaining endothelial cell barrier integrity and to assess the involvement of Smac in an in vivo animal model of HS. HS was induced in urethane‐anesthetized rats by withdrawing blood to reduce the mean arterial pressure to 40 mmHg for one hour followed by resuscitation. FITC‐albumin was given IV during the control period. The mesenteric postcapillary venules in a transilluminated segment of small intestine were examined to quantitate changes in albumin flux using digital microscopy. HS increased microvascular permeability. Ang‐1 pretreatment attenuated HS induced hyperpermeability in comparison to the sham group (p < 0.05). Further, HS significantly increased the cytoplasmic Smac levels compared to the sham group (p < 0.05) and the Ang‐1 pretreatment group (p < 0.05). The present findings suggest that Ang‐1 in addition to being an important regulator of angiogenesis, plays an important role in maintaining endothelial barrier integrity. The protective effects of Ang‐1 on HS‐ induced permeability may be mediated via Smac.