Pioglitazone inhibits oxidative stress, MMP-mediated inflammation and vascular dysfunction in high glucose-induced human saphenous vein grafts
Küçük Resim Yok
Tarih
2023
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier Science Inc
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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 mu M 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 alpha-SMA expression/activity was determined by gelatine zymography/immunohistochemistry. Vascular reactivity to potassium chloride, noradrenaline, serotonin, pros-taglandin F2 alpha 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.
Açıklama
Anahtar Kelimeler
Pioglitazone, Diabetes, Matrix metalloproteinases, Vascular reactivity, Human saphenous vein graft, Matrix Metalloproteinases, Up-Regulation, Artery, Proliferation, Activation, Expression, Receptor, Disease, Injury, Mice
Kaynak
Journal of Diabetes and Its Complications
WoS Q Değeri
Q3
Scopus Q Değeri
Q2
Cilt
37
Sayı
4
