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 with
controls, MMP-9 activity was greater in placental tissue from patients with
PDM and lower in placental tissue from patients with GDM. The modulatory role
of nitric oxide (NO) and reactive oxygen species (ROS) on MMP-9 activity in
placental tissue was evaluated. In healthy placenta, NO synthase inhibitors
diminished MMP-9 activity, whereas NO donors enhanced it. The addition of
xanthine/xanthine oxidase or hydrogen peroxide to placental incubates
enhanced MMP-9 activity, while the addition of superoxide dismutase (SOD)
diminished it. In placental tissue from patients with PDM, MMP-9 activity was
stimulated by NO and by ROS. In placental tissue from patients with PDM,
concentrations of nitrates/nitrites and thiobarbituric acid-reactive
substances (TBARS) were enhanced, whereas SOD activity was decreased,
suggesting that elevated concentrations of NO and ROS may be related to the
enhanced MMP-9 concentrations found in these tissues. In placenta from GDM
patients, in which a diminished concentration of MMP-9 were detected,
nitrate/nitrite concentrations were increased, but placental MMP-9
activity did not change 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 systems and was inhibited by the addition of SOD; however, TBARS and
SOD concentrations were unchanged in these tissues compared with controls.
These findings demonstrate that placental MMP-9 activity is modulated by NO
and ROS and that, in diabetic pathology, NO and ROS may determine changes in
MMP-9 activity, which are probably involved in the structural and functional
abnormalities of diabetic placental tissue.