Hydrogen sulfide (H2S) is now recognized as a third gaseous mediator along with nitric oxide (NO) and carbon monoxide (CO), though it was originally considered as a malodorous and toxic gas. H2S is produced endogenously from cysteine by three enzymes in mammalian tissues. An increasing body of evidence suggests the involvement of H2S in different physiological and pathological processes. Recent studies have shown that H2S has the potential to protect the heart against myocardial infarction, arrhythmia, hypertrophy, fibrosis, ischemia-reperfusion injury, and heart failure. Some mechanisms, such as antioxidative action, preservation of mitochondrial function, reduction of apoptosis, anti-inflammatory responses, angiogenic actions, regulation of ion channel, and interaction with NO, could be responsible for the cardioprotective effect of H2S. Although several mechanisms have been identified, there is a need for further research to identify the specific molecular mechanism of cardioprotection in different cardiac diseases. Therefore, insight into the molecular mechanisms underlying H2S action in the heart may promote the understanding of pathophysiology of cardiac diseases and lead to new therapeutic targets based on modulation of H2S production.

Aims: Myocardial infarction (MI) is a leading cause of death globally. MicroRNAs (miRNAs) have been identified as a novel class of MI injury regulators. Hydrogen sulfide (H 2 S) is a gaseous signaling molecule that regulates cardiovascular function. The purpose of this study was to explore the role of the miR-30 family in protecting against MI injury by regulating H 2 S production. Results: The expression of miR-30 family was upregulated in the murine MI model as well as in the primary cardiomyocyte hypoxic model. However, the cystathionine-c-lyase (CSE) expression was significantly decreased. The overexpression of miR-30 family decreased CSE expression, reduced H 2 S production, and then aggravated hypoxic cardiomyocyte injury. In contrast, silencing the whole miR-30 family can protect against hypoxic cell injury by elevating CSE and H 2 S level. Nonetheless, the protective effect was abolished by cotransfecting with CSE-siRNA. Systemic delivery of a locked nucleic acid (LNA)-miR-30 family inhibitor correspondingly increased CSE and H 2 S level, then reduced infarct size, decreased apoptotic cell number in the peri-infarct region, and improved cardiac function in response to MI. However, these cardioprotective effects were absent in CSE knockout mice. MiR-30b overexpression in vivo aggravated MI injury because of H 2 S reduction, and this could be rescued by Spropargyl-cysteine (SPRC), which is a novel modulator of CSE, or further exacerbated by propargylglycine (PAG), which is a selective inhibitor of CSE. Innovation and Conclusion: Our findings reveal a novel molecular mechanism for endogenous H 2 S production in the heart at the miRNA level and demonstrate the therapeutic potential of miR-30 family inhibition for ischemic heart diseases by increasing H 2 S production. Antioxid. Redox Signal. 22,[224][225][226][227][228][229][230][231][232][233][234][235][236][237][238][239][240]

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Hydrogen sulfide (H2S) has historically been considered to be a toxic gas, an environmental and occupational hazard. However, with the discovery of its presence and enzymatic production through precursors of L-cysteine and homocysteine in mammalian tissues, H2S has recently received much interest as a physiological signaling molecule. H2S is a gaseous messenger molecule that has been implicated in various physiological and pathological processes in mammals, including vascular relaxation, angiogenesis, and the function of ion channels, ischemia/reperfusion (I/R), and heart injury. H2S is an endogenous neuromodulator and present studies show that physiological concentrations of H2S enhance NMDA receptor-mediated responses and aid in the induction of hippocampal long-term potentiation. Moreover, in the field of neuronal protection, physiological concentrations of H2S in mitochondria have many favorable effects on cytoprotection.

Aims: Macrophages are of key importance for tissue repair after myocardial infarction (MI).Hydrogen sulfide (H 2 S) has been shown to exert cardioprotective effects in MI. However, the mechanisms by which H 2 S modulates cardiac remodeling and repair post-MI remain to be clarified. Results: In our current study, we showed H 2 S supplementation ameliorated InnovationWe show here H 2 S supplementation ameliorated pathological remodeling and dysfunction post-MI, accompanied by an increase in M2-polarized macrophages. And we present evidence for a novel mechanism by which macrophage polarization triggered by H 2 S is due to the increase of mitochondrial biogenesis which enhanced lipolysis and fatty acid release, and provided the respiratory substrates for FAO. Our study shows for the first time that H 2 S supplementation, such as H 2 S donors or activators of H 2 S biosynthesis could represent a promising novel therapeutic strategy for MI treatment via stimulation of M2 macrophage polarization.

The present study was designed to investigate whether arsenic trioxide induced the apoptosis in rat mesenteric arterial smooth muscle cells (SMCs), which provides new insights into mechanisms of arsenic-related vascular diseases. Here, we found that arsenic trioxide significantly decreased the viability of SMCs in a dose-dependent manner. In addition, higher level of arsenic trioxide directly caused cellular necrosis. The Hoechst and AO/EB staining demonstrated that apoptotic morphological change was presented in SMCs exposed to arsenic trioxide. The TUNEL assay displayed that more positive apoptotic signal appeared in SMCs treated with arsenic trioxide. The following result showed that ROS formation was markedly increased in arsenic trioxide-treated SMCs. Pretreatment with N-acetylcysteine, an anti-oxidant reagent, obviously attenuated the enhancement of ROS production and the reduction of cell viability induced by arsenic trioxide in SMCs. Arsenic trioxide also enhanced free intracellular Ca(2+) level in SMCs. BAPTA also significantly prevented the increased intracellular Ca(2+) and decreased cell viability induced by arsenic trioxide in SMCs. These results suggested that arsenic trioxide obviously induced apoptosis in SMCs, and its mechanism was partially associated with intracellular ROS formation and free Ca(2+) increasing.

The aim of the study was to investigate the protective effects of sodium hydrosulfide (NaHS), a H2S donor, against hypoxia-induced injury in human umbilical vein endothelial cells (HUVECs) and also to look into the possible mechanisms by which H2S exerts this protective effect. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and scratch wound healing assay were chosen to measure the cell viability and migration-promoting effects. The fluorescent probe, DCFH-DA and 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1) were applied to detect the reactive oxygen species (ROS) level and mitochondrial membrane potential (ΔΨm). Furthermore, western blots were used to measure the expressions of the apoptosis-related proteins. Under hypoxic conditions, 300 μM and 600 μM of H2S could protect HUVECs against hypoxia-induced injury, as determined by MTT assay. Following the treatment of 60 μM NaHS for 18 h, scratch wound healing assays indicated that the scratch became much narrower than control group. After treatment with 60 μM, 120 μM, and 600 μM NaHS, and hypoxia for 30 min, flow cytometry demonstrated that the ROS concentrations decreased to 95.08% ± 5.52%, 73.14% ± 3.36%, and 73.51% ± 3.05%, respectively, compared with the control group. In addition, the JC-1 assay showed NaHS had a protective effect on mitochondria damage. Additionally, NaHS increased Bcl-2 expression and decreased the expression of Bax, Caspase-3 and Caspase-9 in a dose-dependent way. Our results suggest that H2S can protect endothelial cells and promote migration under hypoxic condition in HUVECs. These effects are partially associated with the preservation of mitochondrial function mediated by regulating the mitochondrial-dependent apoptotic pathway.

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