The Effects of TNF-alpha Induction and Alpha Lipoic Acid on Vascular Responses in Human Saphenous Vein
Project no. 20070 · Status: Kapanmış (Yayın bekleniyor) · 2018
Summary
Objective: In coronary artery bypass graft (CABG) surgery, the long-term patency rate of grafts is low because of restenosis due to excessive cytokine release, increased expression/activity of matrix metalloproteinases (MMPs) and oxidative stress. In our study, we aimed to investigate the effects of alpha-lipoic acid (ALA) on oxidative stress, expressions of MMPs, metalloproteinase tissue inhibitor-2 (TIMP-2) and ?-smooth muscle actin (?-SMA) and vascular functional responses in tumor necrosis factor-? (TNF-?)-induced human saphenous vein (HSV) grafts. Materials and Methods: HSV grafts (n=10) taken from patients undergoing CABG operation were divided into 4 rings after the endothelium was removed. The rings were incubated in RPMI containing 20ng/ml TNF-? and/or 2mM ALA for 24 hours. Reactive oxygen species (ROT) levels were determined by chemiluminescence assay. MMP-2, MMP-9 expression/activities were studied by gelatin zymography. Expressions of MMP-14, TIMP-2 and ?-SMA were examined by immunostaining/scoring. Contractile responses to potassium chloride, noradrenaline, serotonin and prostaglandin F2? and relaxation responses to acetylcholine and papaverine were obtained by using isolated organ bath system. Results: TNF-? induced oxidative stress, MMP-2/MMP-14/?-SMA expressions and MMP-2 activity, but decreased TIMP-2 expression. ALA inhibited these effects. TNF-? reduced contractile responses. Similarly, contractile responses significantly reduced in ALA group. However, relaxation effect of ALA was masked in TNF-? plus ALA group. Papaverine relaxations were not changed by TNF-? or ALA. Sensitivity to contractile agents was not affected by either TNF-? or ALA. Conclusion: ALA may contribute to the prevention of graft vasospasm and early graft failure caused by inflammatory processes and oxidative damage.