Protection against endothelial barrier dysfunction through inhibition of the tyrosine kinase abl-related gene (ARG)
The invention relates to the field of endothelial barrier dysfunction, particular, the invention relates to new methods for the treatment of endothelial barrier dysfunction, such as inflammatory edema by inhibiting Abl-related gene (ARG).
1. A method of treating an individual suffering from or at risk of suffering from inflammatory edema, the method comprising:
administering an inhibitor of Abl-related gene (ARG) function to the individual thereby treating said edema in the individual, wherein the inhibitor inhibits or alters the ARG gene, ARG mRNA, or ARG protein.
2. A method according to claim 1 wherein said inflammatory edema is thrombin-induced edema.
3. The method according to claim 1 , wherein the individual is suffering from sepsis, ALI/ARDS, preeclampsia, no reflow stenosis, pulmonary edema, post-radiation pulmonary edema, or post-endarteriectomy pulmonary edema.
4. A method for inhibiting endothelial barrier dysfunction in a collection of endothelial cells comprising an endothelial barrier that dysfunctions or is at risk of dysfunction, said method comprising:
providing said collection of endothelial cells with an inhibitor of Abl-related gene (ARG) function, thereby inhibiting endothelial barrier dysfunction in the collection of endothelial cells,
wherein the inhibitor inhibits or alters the ARG gene, ARG mRNA, or ARG protein.
5. A method of treating an individual suffering from or at risk of suffering from inflammatory edema, the method comprising:
administering an inhibitor of Abl-related gene (ARG) function to the individual thereby treating the edema in the individual,
wherein the inhibitor inhibits alters the ARG gene, ARG mRNA, or ARG protein, and
wherein said inhibitor of Abl-related gene (ARG) function comprises an inhibitor of tyrosine kinase activity of the protein encoded by said Abl-related gene (ARG).
6. A method according to claim 5 , wherein said tyrosine kinase activity inhibitor specifically inhibits the tyrosine kinase activity of the protein encoded by said Abl-related gene (ARG).
7. The method according to claim 5 , wherein said tyrosine kinase activity inhibitor does not significantly inhibit the tyrosine kinase activity of C-kit, PDGFR-alpha, and/or C-Abl.
8. The method according to claim 1 , wherein said inhibitor of Abl-related gene (ARG) function comprises an antisense oligonucleotide specific for a pre-mRNA encoded by said Abl-related gene (ARG).
9. The method according to claim 1 , wherein said inhibitor of Abl-related gene (ARG) function comprises an siRNA specific for mRNA encoded by said Abl-related gene (ARG).
10. The method according to claim 1 , wherein said inhibitor of Abl-related gene (ARG) function is administered for a time period of between 1-20 weeks.
11. The method according to claim 10 , wherein said inhibitor of Abl-related gene (ARG) function is administered to the individual for a time period of between 1-12 weeks.
12. A method of treating an individual diagnosed as suffering from or at risk of suffering from inflammatory edema, the method comprising:
administering an inhibitor of Abl-related gene (ARG) function to the individual thereby treating the edema in the individual,
wherein the inhibitor inhibits or alters the ARG gene, ARG mRNA, or ARG protein.
13. The method according to claim 12 , wherein the inhibitor is administered for a time period of between 1-20 weeks.
14. A method for inhibiting endothelial barrier dysfunction in a collection of endothelial cells comprising an endothelial barrier that dysfunctions or is at risk of dysfunction, the method comprising:
contacting the collection of endothelial cells with an inhibitor of Abl-related gene (ARG) function, thereby inhibiting endothelial barrier dysfunction in the collection of endothelial cells,
wherein the inhibitor inhibits or alters the ARG gene, ARG mRNA, or ARG protein, and
wherein the inhibitor of ARG function comprises an inhibitor of tyrosine kinase activity of the protein encoded by ARG.
15. The method according to claim 14 , wherein the tyrosine kinase activity inhibitor specifically inhibits the tyrosine kinase activity of the protein encoded by ARG.
16. The method according to claim 14 , wherein the tyrosine kinase activity inhibitor does not significantly inhibit the tyrosine kinase activity of C-kit, PDGFR-alpha, and/or C-Abl.
17. The method according to claim 4 , wherein the inhibitor of ARG function comprises an antisense oligonucleotide specific for a pre-mRNA encoded by ARG.
18. The method according to claim 4 , wherein the inhibitor of ARG function comprises an siRNA specific for mRNA encoded by ARG.
19. The method according to claim 4 , wherein the inhibitor of ARG function is provided for between 1 and 20 weeks.
20. The method according to claim 19 , wherein the inhibitor of ARG function is provided for between 1 and 12 weeks.
21. The method according to claim 1 , wherein the inhibitor of ARG function is imatinib or a pharmaceutically acceptable salt thereof.
22. The method according to claim 4 , wherein the inhibitor of ARG function is imatinib or a pharmaceutically acceptable salt thereof.
23. The method according to claim 12 , wherein the inhibitor of ARG function is imatinib or a pharmaceutically acceptable salt thereof.