Effects of Cyclosporine on Metalloproteinase in Endothelial Cells
- E. Ha; K.C. Mun
- Publication Year
- Objectives. Cyclosporine (CsA) is a potent agent widely used after organ transplanta-
tions and in treatment of various autoimmune disorders. Some patients suffer severe
complications including renal and vascular toxicity that are inﬂuenced by the degree of
endothelial damage. Dysregulation of metalloproteinase (MMP) activity is known to
contribute to renal and vascular diseases. To investigate the possible mechanisms of
posttransplantation complications in the kidney and vessels by CsA, we examined its effects
on metalloproteinases in endothelial cells using human umbilical vein endothelial cells
Methods. HUVECs isolated from umbilical cords by collagenase digestion were seeded
in 6-well plates at a density of 1 105
cells/well before treatment with 2–250 mol/L CsA
and a 24-hour incubation. Thereafter we performed gelatin zymography of MMP-1,
MMP-2, MMP-3, MMP-8, MMP-9, and MMp-13 to evaluate band density using a
luminescent image analyzer system with controls calculated as 100%.
Results. MMP-1, MMP-3, MMP-8, MMP-9, and MMP-13 activities were increased
after CsA treatment;MMP-1 121;MMP-3 164;MMP-8 133;MMP-9 124; and
MMP-13 121. In contrast, MMP-2 activity was decreased after CsA treatment;
Conclusions. This study showed CsA to activate most MMPs (except MMP-2) in
endothelial cells. This result suggests that CsA may dysregulate MMPs in endothelial cells.
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