Onursal Ceylan, Reel Buket, Bintepe Caglar, Guzeloglu Mehmet, Ersoy Nevin, Bagriyanik Alper
Ege University, Faculty of Pharmacy, Department of Pharmacology, 35100 Bornova-Izmir, Turkey.
Ege University, Faculty of Pharmacy, Department of Clinical Pharmacy, 35100 Bornova-Izmir, Turkey.
J Diabetes Complications. 2023 Apr;37(4):108421. doi: 10.1016/j.jdiacomp.2023.108421. Epub 2023 Feb 8.
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.
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 F and papaverine was assessed in HSVs.
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.
Pioglitazone may contribute to the prevention of restenosis and maintaining vascular function in HSV grafts of DM patients undergoing CABG.
本研究旨在探讨吡格列酮对高糖（HG）诱导的人隐静脉（HSV）移植物中活性氧（ROS）、基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制因子-2（TIMP-2）的表达/活性，以及血管平滑肌细胞（VSMC）增殖和血管反应性的影响。
从接受冠状动脉旁路移植术（CABG）的患者获取HSV移植物（n = 10），去除内皮后，用30 mM葡萄糖和/或10 μM吡格列酮或0.1%二甲基亚砜（DMSO）孵育24小时。通过化学发光法检测ROS水平，用明胶酶谱法/免疫组织化学法测定MMP-2、-9、-14、TIMP-2和α-平滑肌肌动蛋白（α-SMA）的表达/活性。评估HSV对氯化钾、去甲肾上腺素、5-羟色胺、前列腺素F和罂粟碱的血管反应性。
HG诱导超氧阴离子（SA）水平升高（123%）和其他ROS水平升高（159%），上调MMP-2表达（180%）/活性（79%）、MMP-14表达（24%）和MMP-9活性，同时下调TIMP-2表达（27%）。HG使总MMP-2/TIMP-2比值升高（483%）和MMP-14/TIMP-2比值升高（78%）。然而，HG加吡格列酮可抑制SA（30%）和其他ROS水平（29%），下调MMP-2表达（76%）/活性（83%）、MMP-14表达（38%）和MMP-9活性，同时逆转TIMP-2表达（44%）。HG加吡格列酮降低总MMP-2/TIMP-2比值（91%）和MMP-14/TIMP-2比值（59%）。HG损害对所有药物的收缩反应，但吡格列酮可改善这些反应。
吡格列酮可能有助于预防接受CABG的糖尿病患者HSV移植物的再狭窄并维持血管功能。
