Lung-targeted RNA interference against angiopoietin-2 ameliorates multiple organ dysfunction and death in sepsis

Critical Care Medicine

Volumn 42, Issue 10, 2014, Pages e654-e662

  Stiehl, Thomas ^a   Thamm, Kristina ^a   Kaufmann, Jörg ^b   Schaeper, Ute ^b   Kirsch, Torsten ^a   Haller, Hermann ^a   Santel, Ansgar ^b   Ghosh, Chandra C ^c   Parikh, Samir M ^c   David, Sascha ^a  

^a HANNOVER MEDICAL SCHOOL   (Germany)

^b Silence Therapeutics GmbH   (Germany)

^c HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Angiopoietin 2; Endothelium; Permeability; RNA interference; Sepsis; Small interfering RNA; Tie2

Indexed keywords

ANGIOPOIETIN 2; CELL ADHESION MOLECULE; INTERLEUKIN 6; SMALL INTERFERING RNA; ANGIOPOIETIN RECEPTOR; TEK PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ANTIBODY SPECIFICITY; ARTICLE; DEATH; GENE EXPRESSION; IN VIVO STUDY; LUNG ENDOTHELIUM; MOUSE; MULTIPLE ORGAN FAILURE; NEUTROPHIL CHEMOTAXIS; NONHUMAN; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RNA INTERFERENCE; SEPSIS; ANIMAL; C57BL MOUSE; COMPLICATION; DISEASE MODEL; INFLAMMATION; LUNG; METABOLISM; MORTALITY; PATHOPHYSIOLOGY; PHYSIOLOGY;

ANGIOPOIETIN-2; ANIMALS; DISEASE MODELS, ANIMAL; INFLAMMATION; LUNG; MICE; MICE, INBRED C57BL; MULTIPLE ORGAN FAILURE; RECEPTOR, TIE-2; RNA INTERFERENCE; RNA, SMALL INTERFERING; SEPSIS;

EID: 84914170847     PISSN: 00903493     EISSN: 15300293     Source Type: Journal    
DOI: 10.1097/CCM.0000000000000524     Document Type: Article

References (37)

1. Angus DC, van der Poll T: Severe sepsis and septic shock. N Engl J Med 2013; 369:840-851
2. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000; 342:1301-1308
3. Rivers E, Nguyen B, Havstad S, et al; Early Goal-Directed Therapy Collaborative Group: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368-1377
4. Aird WC: The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 2003; 101:3765-3777
5. Lee WL, Slutsky AS: Sepsis and endothelial permeability. N Engl J Med 2010; 363:689-691
6. Augustin HG, Koh GY, Thurston G, et al: Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Biol 2009; 10:165-177
7. Imhof BA, Aurrand-Lions M: Angiogenesis and infammation face off. Nat Med 2006; 12:171-172
8. Lukasz A, Hellpap J, Horn R, et al: Circulating angiopoietin-1 and angiopoietin-2 in critically ill patients: Development and clinical application of two new immunoassays. Crit Care 2008; 1 2:R94
9. Kümpers P, Lukasz A, David S, et al: Excess circulating angiopoietin-2 is a strong predictor of mortality in critically ill medical patients. Crit Care 2008; 12:R147
10. Parikh SM: Dysregulation of the angiopoietin-Tie-2 axis in sepsis and ARDS. Virulence 2013; 4:517-524
11. Agrawal A, Matthay MA, Kangelaris KN, et al: Plasma angiopoietin-2 predicts the onset of acute lung injury in critically ill patients. Am J Respir Crit Care Med 2013; 187:736-742
12. David S, Mukherjee A, Ghosh CC, et al: Angiopoietin-2 may contribute to multiple organ dysfunction and death in sepsis. Crit Care Med 2012; 40:3034-3041
13. Kurniati NF, van Meurs M, Vom Hagen F, et al: Pleiotropic effects of angiopoietin-2 defciency do not protect mice against endotoxin-induced acute kidney injury. Nephrol Dial Transplant 2013; 28:567-575
14. Ziegler T, Horstkotte J, Schwab C, et al: Angiopoietin 2 mediates microvascular and hemodynamic alterations in sepsis. J Clin Invest 2013; 123:3436-3445
15. Parikh SM, Mammoto T, Schultz A, et al: Excess circulating angiopoietin-2 may contribute to pulmonary vascular leak in sepsis in humans. PLoS Med 2006; 3:e46
16. Strumberg D, Schultheis B, Traugott U, et al: Phase I clinical development of Atu027, a siRNA formulation targeting PKN3 in patients with advanced solid tumors. Int J Clin Pharmacol Ther 2012; 50:76-78
17. Coelho T, Adams D, Silva A, et al: Safety and effcacy of RNAi therapy for transthyretin amyloidosis. N Engl J Med 2013; 369: 819-829
18. Santel A, Aleku M, Röder N, et al: Atu027 prevents pulmonary metastasis in experimental and spontaneous mouse metastasis models. Clin Cancer Res 2010; 16:5469-5480
19. Burnett JC, Rossi JJ: RNA-based therapeutics: Current progress and future prospects. Chem Biol 2012; 19:60-71
20. Fehring V, Schaeper U, Ahrens K, et al: Delivery of therapeutic siRNA to the lung endothelium via novel Lipoplex formulation DACC. Mol Ther 2014; 22:811-820
21. Santel A, Aleku M, Keil O, et al: RNA interference in the mouse vascular endothelium by systemic administration of siRNA-lipoplexes for cancer therapy. Gene Ther 2006; 13:1360-1370
22. Santel A, Aleku M, Keil O, et al: A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium. Gene Ther 2006; 13:1222-1234
23. David S, Ghosh CC, Kümpers P, et al: Effects of a synthetic PEG-ylated Tie-2 agonist peptide on endotoxemic lung injury and mortality. Am J Physiol Lung Cell Mol Physiol 2011; 300: L851-L862
24. Ricci Z, Ronco C: Pulmonary/renal interaction. Curr Opin Crit Care 2010; 16:13-18
25. van Meurs M, Wulfert FM, Knol AJ, et al: Early organ-specifc endothelial activation during hemorrhagic shock and resuscitation. Shock 2008; 29:291-299
26. Takasu O, Gaut JP, Watanabe E, et al: Mechanisms of cardiac and renal dysfunction in patients dying of sepsis. Am J Respir Crit Care Med 2013; 187:509-517
27. David S, von Jan U, Kümpers P, et al: Quantifcation of experimental acute kidney injury by computer-assisted imaging of lectin phytohe-magglutinin E. J Nephrol 2013; 26:385-388
28. Eskandari MK, Bolgos G, Miller C, et al: Anti-tumor necrosis factor antibody therapy fails to prevent lethality after cecal ligation and puncture or endotoxemia. J Immunol 1992; 148:2724-2730
29. David S, Park JK, Meurs MV, et al: Acute administration of recombinant Angiopoietin-1 ameliorates multiple-organ dysfunction syndrome and improves survival in murine sepsis. Cytokine 2011; 55: 251-259
30. David S, Ghosh CC, Kümpers P, et al: Effects of a synthetic PEG-ylated Tie-2 agonist peptide on endotoxemic lung injury and mortality. Am J Physiol Lung Cell Mol Physiol 2011; 300: L851-L862
31. Kim DH, Jung YJ, Lee AS, et al: COMP-angiopoietin-1 decreases lipopolysaccharide-induced acute kidney injury. Kidney Int 2009; 76:1180-1191
32. Vikkula M, Boon LM, Carraway KL 3rd, et al: Vascular dysmorphogen-esis caused by an activating mutation in the receptor tyrosine kinase TIE2. Cell 1996; 87:1181-1190
33. Ward NL, Haninec AL, Van Slyke P, et al: Angiopoietin-1 causes reversible degradation of the portal microcirculation in mice: Implications for treatment of liver disease. Am J Pathol 2004; 165:889-899
34. David S, Kümpers P, van Slyke P, et al: Mending leaky blood vessels: The angiopoietin-Tie2 pathway in sepsis. J Pharmacol Exp Ther 2013; 345:2-6
35. Faubel S: Pulmonary complications after acute kidney injury. Adv Chronic Kidney Dis 2008; 15:284-296
36. Klein CL, Hoke TS, Fang WF, et al: Interleukin-6 mediates lung injury following ischemic acute kidney injury or bilateral nephrectomy. Kidney Int 2008; 74:901-909
37. Grams ME, Rabb H: The distant organ effects of acute kidney injury. Kidney Int 2012; 81:942-948