Abstract
BackgroundHydrogen sulfide (H2S) has been shown to have cytoprotective effects in models of hypertension, ischemia/reperfusion and Alzheimer's disease. However, little is known about its effects or mechanisms of action in atherosclerosis. Therefore, in the current study we evaluated the pharmacological effects of H2S on antioxidant defenses and mitochondria protection against hydrogen peroxide (H2O2) induced endothelial cells damage.Methodology and Principal FindingsH2S, at non-cytotoxic levels, exerts a concentration dependent protective effect in human umbilical vein endothelial cells (HUVECs) exposed to H2O2. Analysis of ATP synthesis, mitochondrial membrane potential (ΔΨm) and cytochrome c release from mitochondria indicated that mitochondrial function was preserved by pretreatment with H2S. In contrast, in H2O2 exposed endothelial cells mitochondria appeared swollen or ruptured. In additional experiments, H2S was also found to preserve the activities and protein expressions levels of the antioxidants enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in H2O2 exposed cells. ROS and lipid peroxidation, as assessed by measuring H2DCFDA, dihydroethidium (DHE), diphenyl-l-pyrenylphosphine (DPPP) and malonaldehyde (MDA) levels, were also inhibited by H2S treatment. Interestingly, in the current model, D, L-propargylglycine (PAG), a selective inhibitor of cystathionine γ-lyase (CSE), abolished the protective effects of H2S donors.InnovationThis study is the first to show that H2S can inhibit H2O2 mediated mitochondrial dysfunction in human endothelial cells by preserving antioxidant defences.SignificanceH2S may protect against atherosclerosis by preventing H2O2 induced injury to endothelial cells. These effects appear to be mediated via the preservation of mitochondrial function and by reducing the deleterious effects of oxidative stress.
Highlights
Atherosclerosis is a chronic inflammatory response to high serum cholesterol levels, leading to plaques formation and the hardening of arteries
NaHS is non-toxic to human umbilical vein endothelial cells (HUVECs) Sodium hydrosulfide (NaHS) at concentrations of 10, 30, 100, 300 and 500 mM was found to be non-toxic to endothelial cells, as determined by the MTT viability assay (Fig 1 A, n = 9)
This study explored the cardiovascular protective effects by H2S on H2O2 induced injured in HUVECs as assessed by measurements of mitochondrial integrity and antioxidative systems
Summary
Atherosclerosis is a chronic inflammatory response to high serum cholesterol levels, leading to plaques formation and the hardening of arteries. These effects increase an individuals risk of stroke, myocardial infarction or additional systemic complications [1]. The progressive nature of this disease, that can remain undetected for many years, is induced and maintained by several mechanisms including oxidative stress, inflammation, cell adhesion and cellular proliferation [2]. These combined changes lead to endothelial dysfunction. In the current study we evaluated the pharmacological effects of H2S on antioxidant defenses and mitochondria protection against hydrogen peroxide (H2O2) induced endothelial cells damage
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