Angiotensin-converting enzyme inhibitors attenuate propofol-induced pro-oxidative and antifibrinolytic effect in human endothelial cells

Abstract

Introduction:The aim of this study was to investigate the effects of plasma and tissue angiotensin-converting enzyme inhibitors (ACE-Is) against propofol-induced endothelial dysfunction and to elucidate the involved mechanisms in vitro.Materials and methods:We examined the effects of propofol (50 μM), quinaprilat and enalaprilat (10−5 M) on fibrinolysis (t-PA, PAI-1, TAFI antigen levels), oxidative stress parameters (H2O2 and MDA antigen levels and SOD and NADPH oxidase mRNA levels) and nitric oxide bioavailability (NO2/NO3 concentration and NOS expression at the level of mRNA) in human umbilical vein endothelial cells (HUVECs).Results:We found that both ACE-Is promoted similar endothelial fibrinolytic properties and decreased oxidative stress in vitro. Propofol alone increased the release of antifibrinolytic and pro-oxidative factors from the endothelium and increased mRNA iNOS expression. We also found that the incubation of HUVECs in the presence of propofol following ACE-Is pre-incubation caused weakness of the antifibrinolytic and pro-oxidative potential of propofol and this effect was similar after both ACE-Is.Conclusions:This observation suggests that the studied ACE-Is exerted protective effects against endothelial cell dysfunction caused by propofol, independently of hemodynamics.

Peroxisome proliferator-activated receptor α attenuates high-cholesterol diet-induced toxicity and pro-thrombotic effects in mice

“…Next, we investigated the effect of the HC diet-feeding on serum and liver levels of the anti-coagulation and antiplatelet molecules, sulfatides, which are also regulated by PPARα, in WT and Ppara -null mice (Marx et al 2001; Kimura et al 2012; Masuda et al 2012; Kanbe et al 2014; Gonsalves et al 2015; Wojewodzka-Zelezniakowicz et al 2017). Liver and serum levels of sulfatides were similar between WT and Ppara -null mice fed with the control diet, and these levels became markedly lower in mice of either genotype fed the HC diet.…”

“…It was reported that the HC diet increases oxidative stress (Naziroglu et al 2014). Indeed, levels of the thrombotic factors TF, PAI-1, and sulfatides are influenced by oxidative stress (Marx et al 2001; Kimura et al 2012; Masuda et al 2012; Kanbe et al 2014; Gonsalves et al 2015; Wojewodzka-Zelezniakowicz et al 2017), and that PPARα exerts anti-oxidative effects (Kamijo et al 2007). Therefore, we investigated the effects of feeding the HC diet on hepatic oxidative stress and the related factors in WT and Ppara -null mice.…”

“…Our previous experimental and clinical studies have demonstrated that serum sulfatides exert anti-coagulative and anti-platelet functions, and that lower levels of serum sulfatides might be associated with the development of CVD (Kamijo et al 2012; Kimura et al 2012; Yuzhe et al 2015). It was reported that expression of these important molecules (TF, PAI-1, CPB2, and sulfatides) is regulated by PPARα and oxidative stress (Marx et al 2001; Kimura et al 2012; Masuda et al 2012; Kanbe et al 2014; Gonsalves et al 2015; Wojewodzka-Zelezniakowicz et al 2017). We hypothesized that a HC diet exerts its toxic effects through changes in lipid metabolism, oxidative stress, and production of these thrombosis-related factors, and that PPARα might strongly influence such effects, thereby modulating development of CVD.…”

Hyperglycemia Potentiates Prothrombotic Effect of Aldosterone in a Rat Arterial Thrombosis Model

“…After 2 h of incubation, cell supernatants were collected, and TF, t-PA, PAI-I, NO 2 /NO 3 , H 2 O 2 , and MDA levels were measured with commercially available kits. Endothelial nitric oxide synthase (eNOS) expression at the mRNA level was determined by quantitative real-time PCR as previously described [ 9 , 34 ]. The following PCR primers were designed: 5′-CATCGGCGTGCTGCGGGATCAG-3′ and 5′-GGGCTGTTGGTGTCTGAGCCGG-3′, which were specific for the mRNAs of eNOS.…”

Reactive Oxygen Species Scavenging Nanomedicine for the Treatment of Ischemic Heart Disease

“…Enalapril 1) Enhances GSH [118] 2) Scavenges ROS [119] Captopril 1) Enhances GSH [118] 2) Protects EC from H 2 O 2 through AKT/mTOR pathway [120] 3) Suppresses NOX expression [121] 4) Scavenges ROS [119] Quinaprilat 1) Decreases H 2 O 2 and MDA induced by propofol [122] Enalaprilat 1) Decreases H 2 O 2 induced by propofol [122] 2) Increases SOD activity and reduces the thiobarbituric acid reactive substances level [144] Lisinopril 1) Reduces Superoxide and hydroxyl radical in diabetic myocardium [145] 2) Reduces serum markers of oxidative stress [146] Perindopril 1) Increases eNOS expression and activity [147] 2) Increases NO [147] Angiotensin II receptor blockers Irbesartan 1) Reduces superoxide and p22phox [126,148] 2) Increases NO bioavailability [148] 3) Increases GSH and SOD activity [149] Olmesartan 1) Reduces as 8-epi-prostaglandin F2α (8-epi-PGF2α) and 8-hydroxydeoxyguanosine (OHdG) [125] 2) Reduces ROS production [150] 3) Enhances NO release [151] Azilsartan 1) Improves eNOS activity and reduces NOX2 and NOX4 expression [127] 2) Restores uncoupled eNOS [127] 3) Inhibits NOX2 and NOX4 [127] Valsartan 1) Reduces 8-epi-PGF2α and OHdG [125] 2) Reduces ROS generated by polymorphonuclear cells and mononuclear cells [128,152] 3) Promotes NO synthesis [153] Calcium channel blockers Amlodipine 1) Enhances NO formation and increases NO bioavailability [130] 2) Promotes the unclamping of eNOS from caveolin to potentiate NO production [154] 3) Reduces O 2 − and ONOO − production [155] Benidipine 1) Inhibits ROS production [131] 2) Decreases oxidative stress in polymorphonuclear cells [156] Lacidipine 1) Reduces the ox-LDL induced ROS [129a]…”