Angiopoietin-1 reduces iopromide-induced endothelial cell apoptosis through activation of phosphatidylinositol 3'-kinase/p70 S6 kinase.
Radiocontrast media can induce vascular endothelial cell apoptosis. Apoptotic damage to the vascular endothelium is an important mechanism in vascular disease. Several growth factors with anti-apoptotic effects may help protect the vascular endothelium from apoptosis. The present study evaluated whether the radiocontrast agent iopromide induces apoptosis in human umbilical vein endothelial cells and also whether angiopoietin-1 (Ang1) protects against iopromide-induced apoptosis through the p70 S6 kinase-dependent signaling pathway. Iopromide induced apoptosis in vascular endothelial cells in a dose-dependent manner. Ang1 reduced iopromide-induced apoptosis in a dose-dependent manner. Wortmannin and LY294002, phosphatidylinositol 3'-kinase inhibitors, decreased the Ang1-induced anti-apoptotic effect. Ang1 mediates the activation of mTOR/ribosomal protein p70 S6 kinase through phosphatidylinositol-3' kinase. Wortmannin and rapamycin, an inhibitor of mTOR, suppressed Ang1-induced p70 S6 kinase phosphorylation and partially inhibited the Ang1-induced anti-apoptotic effect. These results suggest that Ang1 may protect vascular endothelial cells from iopromide-induced apoptosis through phosphatidylinositol 3'-kinase and mTOR/S6 kinase. Pretreatment with Ang1 could help maintain normal vascular endothelial cell integrity before and during systemic radiocontrast administration.
Moon
S O
SO
Renal Regeneration Laboratory and Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Korea.
Kim
W
W
Kim
D H
DH
Sung
M J
MJ
Lee
S
S
Kang
K P
KP
Yi
A S
AS
Jang
K Y
KY
Lee
S Y
SY
Park
S K
SK
D000704:Analysis of Variance; D042683:Angiopoietin-1 / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003287:Contrast Media / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007472:Iohexol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008353:Mannitol / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology
D042683:Angiopoietin-1; D003287:Contrast Media; D008353:Mannitol; D007472:Iohexol; C038192:iopromide; D019869:Phosphatidylinositol 3-Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa