Sevoflurane pretreatment attenuates TNF-α-induced human endothelial cell dysfunction through activating eNOS/NO pathway

Abstract

Endothelial dysfunction induced by oxidative stress and inflammation plays a critical role in the pathogenesis of cardiovascular diseases. The anesthetic sevoflurane confers cytoprotective effects through its anti-inflammatory properties in various pathologies such as systemic inflammatory response syndrome and ischemic-reperfusion injury but mechanism is unclear. We hypothesized that sevoflurane can protect against tumor necrosis factor (TNF)-α-induced endothelial dysfunction through promoting the production of endothelium-dependent nitric oxide (NO). Primary cultured human umbilical vein endothelial cells (HUVECs) were pretreated with different concentrations (0.5, 1.5 and 2.5 minimum alveolar concentration, MAC) of sevoflurane for 30 min before TNF-α (10 ng/mL) stimulation for 4 h. Sevoflurane pretreatment significantly reduced TNF-α-induced VCAM-1, ICAM-1, IκBα, and NF-κB activation, and blocked leukocytes adhesion to HUVECs. Meanwhile, sevoflurane (1.5 and 2.5 MAC) significantly induced endothelial nitric oxide synthase (eNOS) phosphorylation and enhanced NO levels both intracellularly and in the cell culture medium. All these cytoprotective effects of sevoflurane were abrogated by NG-nitro-l-arginine methyl ester (l-NAME), a non-specific nitric oxide synthase inhibitor. Collectively, these data indicate that sevoflurane protects against TNF-α -induced vascular endothelium dysfunction through activation of eNOS/NO pathway and inhibition of NF-κB.

Liraglutide mitigates TNF‐α induced pro‐atherogenic changes and microvesicle release in HUVEC from diabetic women

“…Similarly to MAPK, NF‐kB activation shows a peak 30 to 60 minutes after TNF‐α exposure; then, it progressively declines while the effects of its activation on adhesion molecules expression can be observed a few hours later …”

“…It is however entirely possible (and indeed very likely) that right after TNF-α stimulation an increase in MAPK activation occurred which is not anymore detectable at the time of our observation. This could still explain the more pronounced effect of TNF-α on VCAM-1 and ICAM-1 total protein levels and membrane exposure as observed in GD-HUVEC 16 hours after stimulation.Similarly to MAPK, NF-kB activation shows a peak 30 to 60 minutes after TNF-α exposure; then, it progressively declines while the effects of its activation on adhesion molecules expression can be observed a few hours later 38. It should however be considered that MAPK and NF-kB activation might be just a part of the story.…”

Myocardial ischaemia reperfusion injury: the challenge of translating ischaemic and anaesthetic protection from animal models to humans

“…We have recently shown that sevoflurane pre-treatment protects against TNF-α-induced vascular endothelial dysfunction, through activation of the eNOS/NO pathway and inhibition of NF-κB. 130 Sevoflurane may also protect against liver injury in patients undergoing cardiac surgery. [131][132][133][134] Exogenous opioids have also been shown to confer systemic multi-organ protection.…”

Sevoflurane postconditioning attenuates cardiomyocyte hypoxia/reoxygenation injury via restoring mitochondrial morphology

“…SPostC has been shown to enhance endothelial and cardiac resistance to IRI both in experimental (Li et al, 2015) and in clinical settings (Wang et al, 2013). While some factors have been linked to the protective effects of SPostC, the underlying mitochondrial-related mechanism is not fully understood.…”