The Anti-apoptotic Effect of Adrenomedullin on Vascular Endothelial Cells in Radiocontrast Media-induced Apoptosis / 대한신장학회지

PURPOSE: Because vascular endothelial cells play a pivotal role in the vascular diseases, damage of vascular endothelial cells lead to progression of vascular disease. Apoptotic damage of cells is an important mechanism in vascular disease. Therefore, several growth factors that have antiapoptotic effect may have a protective role in maintaining a cell function in apoptotic cell injury. In this study, we examined the effects of adrenomedullin on apoptosis in iopromide-induced endothelial cell injury. METHODS: Human umbilical vein endothelial cells were incubated with nonionic radiocontrast agent, iopromide and/or adrenomedullin. Apoptosis was assessed quantitatively using FACScan after annexin V-FITC and propidium iodide staining, and by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) stain. Signaling pathway was evaluated by Western blot analysis of phospho-Akt and Akt. RESULTS: Iopromide-induced apoptosis in human umbilical vein endothelial cells was increased in a dose-dependent manner. Adrenomedullin prevented iopromide-induced apoptosis in human umbilical vein endothelial cells in a dose dependent manner. Wortmannin, phosphatidylinositol 3-kinase inhibitor, decrease the adrenomedullin-induced antiapoptotic effect. CONCLUSION: These results suggest that adrenomedullin protects vascular endothelial cells from iopromide-induced apoptosis by regulating the activity of Akt.

Apoptotic Effect of Radiocontrast Media on Human Umbilical Vein Endothelial Cells

The damage of vascular endothelial cells leads to the progression of vascular disease. Apoptotic damage of endothelial cells is an important mechanism in vascular disease. Recently, it has been reported that radiocontrast can induce vascular endothelial cell injury. The present study used terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and FACScan analysis to examine whether radiocontrast agenst, such as iopromide, sodium-meglumine-ioxithalamate or gadopentetate dimeglumine, induce apoptotic injury in human umbilical vein endothelial cells. In the study, iopromide, sodium-meglumine-ioxithalamate and gadopentetate dimeglumine brought about human umbilical vein endothelial cell death in phase-contrast microscopic findings. According to TUNEL and FACScan analysis, iopromide and sodium-meglumine- ioxithalamate induced apoptosis in vascular endothelial cells in a dose-dependent. The apoptotic effect of sodium-meglumine-ioxithalamate was shown to be greater than that of iopromide. Gadopentetate dimeglumine also induced apoptosis in human umbilical vein endothelial cells as observed by TUNEL and FACScan analysis. These results suggest that iopromide, which is a non-ionic radiocontrast agent, proved to be less apoptotic than sodium-meglumine-ioxithalamate. Gadopentetate dimeglumine, which is used MRI, has an apoptotic effect in vascular endothelial cells. Thus, apoptosis of endothelial cells by radiocontrast agents might induce deleterious effects on vascular endothelial integrity.

The Antiapoptotic Effect of Vascular Endothelial Growth Factor and Angiopoietin-1 on Glomerular Endothelial Cells in Adriamycin or Cisplatin-induced Apoptosis / 대한신장학회잡지

BACKGROUND: Because glomerular endothelium play a pivotal role in the renal diseases, damage of glomerular endothelial cells lead to progression of glomerular sclerosis and decrement of renal function. Apoptotic damage of cells is an important mechanism in renal disease. Therefore, several growth factors that have antiapoptotic effect may have a protective role in maintaining a renal function in apoptotic cell injury. METHODS: The present study evaluated whether cisplatin or adriamycin induce apoptosis in glomerular endothelial cells. We also evaluated the antiapoptotic effect of angiopoietin-1 and VEGF in cisplatin or adriamycin- induced apoptosis. RESULTS: Cisplatin or adriamycin induced apoptosis in glomerualr endothelial cell in dose dependent manner. Angiopoietin-1 and VEGF produced antiapoptotic effect in cisplatin or adriamycin-induced apoptosis in a dose dependent manner. The antiapoptotic effect of angiopoietin-1 was more potent than that of VEGF in glomerualr endothelial cells. Wortmannin, a phosphatidylinositol 3'-kinase inhibitor decrease the angiopoietin-1 or VEGF-induced antiapoptotic effect. CONCLUSION: These results suggest that angiopoietin-1 and VEGF may be a strong survival factor for the glomerular endothelial cells in the cisplatin or adriamycin-induced apoptosis through phosphatidylinositol 3'-kinase/Akt. Therefore, pretreatment of angiopoietin-1 and VEGF could play a beneficial role for maintaining normal glomerular endothelial cell integrity before and during systemic cisplatin or adriamycin therapy.