Membrane-type matrix metalloproteinase-9 activity in placental tissue frompatients with pre-existing and gestational diabetes mellitus

The activity of matrix metalloproteinase (MMP)-9 was evaluated in placental tissue from healthy subjects (controls) and from patients with gestational and pre-existing diabetes mellitus (GDM and PDM, respectively). Compared w ith controls, MMP-9 activity was greater in placental tissue from patients with PDM and lower in placental tissue from patients with GDM. The modulato ry role of nitric oxide (NO) and reactive oxygen species (ROS) on MMP-9 act ivity in placental tissue was evaluated. In healthy placenta, NO synthase i nhibitors diminished MMP-9 activity, whereas NO donors enhanced it. The add ition of xanthine/xanthine oxidase or hydrogen peroxide to placental incuba tes enhanced MMP-9 activity, while the addition of superoxide dismutase (SO D) diminished it. In placental tissue from patients with PDM, MMP-9 activit y was stimulated by NO and by ROS. In placental tissue from patients with P DM, concentrations of nitrates/nitrites and thiobarbituric acid-reactive su bstances (TBARS) were enhanced, whereas SOD activity was decreased, suggest ing that elevated concentrations of NO and ROS may be related to the enhanc ed MMP-9 concentrations found in these tissues. In placenta from GDM patien ts, in which a diminished concentration of MMP-9 were detected, nitrate/nit rite concentrations were increased, but placental MMP-9 activity did not ch ange in the presence of either NO donors or inhibitors. The activity of MMP -9 in placental tissue from patients with GDM was stimulated by ROS donor s ystems and was inhibited by the addition of SOD; however, TBARS and SOD con centrations were unchanged in these tissues compared with controls. These f indings demonstrate that placental MMP-9 activity is modulated by NO and RO S and that, in diabetic pathology, NO and ROS may determine changes in MMP- 9 activity, which are probably involved in the structural and functional ab normalities of diabetic placental tissue.