Gonzalez, ET; Gimeno, M; Micone, P; Baier, M; Pesaresi, M; Sinner, D; Jawerbaum, A; Pustovrh, C
Abstract:
The activity of matrix metalloproteinase (MMP)-9 was evaluated in placentaltissue from healthy subjects (controls) and from patients with gestational andpre-existing diabetes mellitus (GDM and PDM, respectively). Compared withcontrols, MMP-9 activity was greater in placental tissue from patients withPDM and lower in placental tissue from patients with GDM. The modulatory roleof nitric oxide (NO) and reactive oxygen species (ROS) on MMP-9 activity inplacental tissue was evaluated. In healthy placenta, NO synthase inhibitorsdiminished MMP-9 activity, whereas NO donors enhanced it. The addition ofxanthine/xanthine oxidase or hydrogen peroxide to placental incubatesenhanced MMP-9 activity, while the addition of superoxide dismutase (SOD)diminished it. In placental tissue from patients with PDM, MMP-9 activity wasstimulated by NO and by ROS. In placental tissue from patients with PDM,concentrations of nitrates/nitrites and thiobarbituric acid-reactivesubstances (TBARS) were enhanced, whereas SOD activity was decreased,suggesting that elevated concentrations of NO and ROS may be related to theenhanced MMP-9 concentrations found in these tissues. In placenta from GDMpatients, in which a diminished concentration of MMP-9 were detected,nitrate/nitrite concentrations were increased, but placental MMP-9activity did not change in the presence of either NO donors or inhibitors. Theactivity of MMP-9 in placental tissue from patients with GDM was stimulated byROS donor systems and was inhibited by the addition of SOD; however, TBARS andSOD concentrations were unchanged in these tissues compared with controls.These findings demonstrate that placental MMP-9 activity is modulated by NOand ROS and that, in diabetic pathology, NO and ROS may determine changes inMMP-9 activity, which are probably involved in the structural and functionalabnormalities of diabetic placental tissue.