Protective Role of Angiopoietin-1 in Endotoxic Shock
Key result
Pretreatment with AdhAng1 preserved blood pressure (76 vs 49 mm Hg, P<0.05) and cardiac output, reduced lung injury, and improved survival in a murine model of endotoxic shock.
Why the study?
Does an adenoviral construct expressing human Ang1 improve hemodynamics and survival in a murine model of LPS-induced endotoxic shock?
Population
C57BL/6 mice with lipopolysaccharide (LPS)-induced endotoxic shock
Comparison
Intravenous application of 1.0x10^9… vs Intravenous application of an identical vector…
Design
Preclinical
Follow-up
12 hours (for hemodynamic assessment)
Authors
Discussion
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Member takes
Implication
Ang1 attenuates murine endotoxic shock; leaves open translation to human sepsis trials.
Key Points
- To examine the therapeutic efficacy and protective mechanisms of angiopoietin-1 in a murine model of lipopolysaccharide-induced endotoxic shock.
- Endotoxic shock was induced in C57BL/6 mice via intraperitoneal lipopolysaccharide (LPS) injection.
- Mice were pretreated with an intravenous injection of 1.0x10^9 plaque-forming units of an adenoviral vector expressing human Ang1 (AdhAng1) or a control vector expressing green fluorescent protein (AdGFP).
- Hemodynamic function, Kaplan-Meier survival, lung histopathology, lung water content, inflammatory markers, and pulmonary endothelial nitric oxide synthase (eNOS) expression were evaluated.
- AdhAng1 mice showed significantly preserved hemodynamic parameters 12 hours post-LPS compared to AdGFP controls, including blood pressure (76+/-3 vs 49+/-7 mm Hg), dP/dt_max (5091+/-489 vs 2699+/-233 mm Hg/s), and cardiac output (6.7+/-1.4 vs 2.8+/-0.8 mL/min; P<0.05).
- Ang1 gene delivery significantly increased overall Kaplan-Meier survival, attenuated lung injury, and reduced lung water content and myeloperoxidase activity.
- Expression of vascular adhesion molecules (VCAM-1, ICAM-1, E-selectin) was reduced, while pulmonary eNOS expression and activity were preserved in AdhAng1 mice.
Structured PICO
Does an adenoviral construct expressing human Ang1 improve hemodynamics and survival in a murine model of LPS-induced endotoxic shock?
P
Population
C57BL/6 mice subjected to a murine model of lipopolysaccharide (LPS)-induced endotoxic shock.
I
Intervention
Intravenous application of 1.0x10^9 plaque-forming units of an adenoviral construct expressing human Angiopoietin-1 (AdhAng1)
C
Comparator
Intravenous application of an identical vector expressing green fluorescent protein (AdGFP)
O
Outcome
Hemodynamic function (blood pressure, dP/dtmax, cardiac output) at 12 hours after LPS injection, and Kaplan-Meier survival ratesurrogate
Main Result
Absolute Event Rate: 76% vs 49%
p-value: p=<0.05
Pretreatment with an adenoviral construct encoding Ang1 improves hemodynamics, reduces lung injury, and enhances survival in a murine model of endotoxic shock.
Cite This Study
Witzenbichler et al. (2004) studied Endotoxic shock. Adenoviral construct expressing human Ang1 (AdhAng1) vs. Adenoviral vector expressing green fluorescent protein (AdGFP) was evaluated on Blood pressure at 12 hours after LPS injection (mm Hg) (p=<0.05). Pretreatment with AdhAng1 preserved blood pressure (76 vs 49 mm Hg, P<0.05) and cardiac output, reduced lung injury, and improved survival in a murine model of endotoxic shock.