Pioglitazone inhibits oxidative stress, MMP-mediated inflammation and vascular dysfunction in high glucose-induced human saphenous vein grafts

Onursal C., Reel B., Bintepe C., Guzeloglu M., Ersoy N., BAĞRIYANIK H. A.

Journal of Diabetes and its Complications, vol.37, no.4, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 37 Issue: 4
  • Publication Date: 2023
  • Doi Number: 10.1016/j.jdiacomp.2023.108421
  • Journal Name: Journal of Diabetes and its Complications
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CINAHL, EMBASE, MEDLINE
  • Keywords: Diabetes, Human saphenous vein graft, Matrix metalloproteinases, Pioglitazone, Vascular reactivity
  • Dokuz Eylül University Affiliated: Yes


Aims: The aim of this study was to investigate the effects of pioglitazone on reactive oxygen species (ROS), expressions/activities of MMPs and TIMP-2, and VSMC proliferation and vascular reactivity in high glucose (HG)-induced human saphenous vein (HSV) grafts. Methods: HSV grafts (n = 10) obtained from patients undergoing CABG were incubated with 30 mM glucose and/or 10 μM pioglitazone or 0.1 % DMSO for 24 h after endothelium removal. ROS levels were examined by chemiluminescence assay, MMP-2,-9,-14, TIMP-2, and α-SMA expression/activity was determined by gelatine zymography/immunohistochemistry. Vascular reactivity to potassium chloride, noradrenaline, serotonin, prostaglandin F2α and papaverine was assessed in HSVs. Results: HG induced superoxide anion (SA) (123 %) and other ROS levels (159 %), up-regulated MMP-2 expression (180 %)/activity (79 %), MMP-14 expression (24 %) and MMP-9 activity while down-regulating TIMP-2 expression (27 %). HG elevated total MMP-2/TIMP-2 ratio (483 %) and MMP-14/TIMP-2 ratio (78 %). However, HG plus pioglitazone inhibited SA (30 %) and other ROS levels (29 %), down-regulated MMP-2 expression (76 %)/activity (83 %), MMP-14 expression (38 %) and MMP-9 activity, while reversing TIMP-2 expression (44 %). HG plus pioglitazone decreased total MMP-2/TIMP-2 ratio (91 %) and MMP-14/TIMP-2 ratio (59 %). HG impaired contractions to all agents but pioglitazone improved them. Conclusions: Pioglitazone may contribute to the prevention of restenosis and maintaining vascular function in HSV grafts of DM patients undergoing CABG.