Hydrogen sulfide: A new therapeutic target in vascular diseases

Zhu, Cuilin; Liu, Qing; Li, Xin; Wei, Ran; Ge, Tongtong; Zheng, Xin; Li, Bingjin; Liu, Kexiang; Cui, Ranji

doi:10.3389/fendo.2022.934231

Cited by 16 publications

(5 citation statements)

References 119 publications

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“…This epigenetic alteration leads to an imbalance in the transsulfuration pathway as it reduces the conversion of homocysteine into cysteine, with the subsequent development of hyperhomocysteinemia, a recognized risk factor for vascular diseases [94,95]. At the same time, the reduced expression of CBS leads to a deficient biosynthesis of H 2 S. Which of hyperhomocysteinemia, impaired biosynthesis of H 2 S, or both is directly involved in the onset and progression of vascular diseases is not well established, but many studies support the use of compounds targeting the "H 2 S-system" in the treatment of hypertension [24,96], mainly due to the antihypertensive effects of the gasotransmitter [97] and its emerging role in the regulation of epigenetic mechanisms [98]. In addition, the impaired biosynthesis of H 2 S in patients with hypertension confirms the potential use of the sulfur gasotransmitter as a biomarker of the disease.…”

Section: Discussionmentioning

confidence: 99%

Circulating Levels of Hydrogen Sulfide (H2S) in Patients with Age-Related Diseases: A Systematic Review and Meta-Analysis

et al. 2023

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Hydrogen sulfide (H2S) is an endogenous gasotransmitter that promotes multiple biological effects in many organs and tissues. An imbalanced biosynthesis of H2S has been observed in animal models of age-related pathological conditions. However, the results from human studies are inconsistent. We performed a systematic review with meta-analysis of studies searched in Medline, Embase, Scopus, and CENTRAL databases. We included observational studies on patients with age-related diseases showing levels of H2S in blood, plasma, or serum. All the analyses were carried out with R software. 31 studies were included in the systematic review and 21 in the meta-analysis. The circulating levels of H2S were significantly reduced in patients with progressive, chronic, and degenerative diseases compared with healthy people (standardized mean difference, SMD: −1.25; 95% confidence interval, CI: −1.98; −0.52). When we stratified results by type of disorder, we observed a significant reduction in circulating levels of H2S in patients with vascular disease (e.g., hypertension) (SMD: −1.32; 95% CI: −2.43; −0.22) or kidney disease (SMD: −2.24; 95% CI: −4.40; −0.08) compared with the control group. These results could support the potential use of compounds targeting the “H2S system” to slow down the progression of many diseases in the elderly.

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Section: Discussionmentioning

confidence: 99%

Circulating Levels of Hydrogen Sulfide (H2S) in Patients with Age-Related Diseases: A Systematic Review and Meta-Analysis

et al. 2023

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“…Because of its lipophilicity, H 2 S gas can easily diffuse through cell membranes independently from receptors and cause various local and systemic effects [ 30 ]. H 2 S is closely linked to several vascular diseases and is used as a new therapeutic target [ 31 ]. H 2 S is involved in the regulation of various physiological and pathological conditions in cardiovascular [ 32 ], renal [ 33 ], and central nervous systems [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Hydrogen Sulfide on Essential Functions of Polymorphonuclear Leukocytes

Farahat

Kherkheulidze

Nopp

et al. 2023

Toxins

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Impaired polymorphonuclear leukocyte (PMNL) functions contribute to increased infections and cardiovascular diseases in chronic kidney disease (CKD). Uremic toxins reduce hydrogen sulfide (H2S) levels and the anti-oxidant and anti-inflammatory effects of H2S. Its biosynthesis occurs as a side process of transsulfuration and in the disposal of adenosylhomocysteine, a transmethylation inhibitor and proposed uremic toxin. PMNL chemotaxis was measured by the under-agarose method, phagocytosis, and oxidative burst by flow cytometry in whole blood and apoptosis by determining DNA content by flow cytometry and morphological features by fluorescence microscopy. Sodium hydrogen sulfide (NaHS), diallyl trisulphide (DATS) and diallyl disulphide (DADS), cysteine, and GYY4137 were used as H2S-producing substances. Increased H2S concentrations did not affect chemotaxis and phagocytosis. NaHS primed PMNL oxidative burst activated by phorbol 12-myristate 13-acetate (PMA) or E. coli. Both DATS and cysteine significantly decreased E. coli-activated oxidative burst but had no effect on PMA stimulation. While NaHS, DADS, and cysteine attenuated PMNL apoptosis, GYY4137 decreased their viability. Experiments with signal transduction inhibitors suggest that the intrinsic apoptosis pathway is mainly involved in GYY4137-induced PMNL apoptosis and that GYY4137 and cysteine target signaling downstream of phosphoinositide 3-kinase.

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“…H 2 S has been shown to inhibit the activation of NF-κB in endothelial cells and macrophages by suppressing the phosphorylation and degradation of IκBα, an inhibitor of NF-κB. This inhibition leads to reduced production of proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α [73]. In addition, H 2 S has been shown to enhance the expression and activity of nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that regulates the expression of antioxidant and cytoprotective genes [74].…”

Section: Inflammation In Atherosclerosis and The Role Of Hydrogen Sul...mentioning

confidence: 99%

Hydrogen Sulfide and Oxygen Homeostasis in Atherosclerosis: A Systematic Review from Molecular Biology to Therapeutic Perspectives

Munteanu

2023

IJMS

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Atherosclerosis is a complex pathological condition marked by the accumulation of lipids in the arterial wall, leading to the development of plaques that can eventually rupture and cause thrombotic events. In recent years, hydrogen sulfide (H2S) has emerged as a key mediator of cardiovascular homeostasis, with potential therapeutic applications in atherosclerosis. This systematic review highlights the importance of understanding the complex interplay between H2S, oxygen homeostasis, and atherosclerosis and suggests that targeting H2S signaling pathways may offer new avenues for treating and preventing this condition. Oxygen homeostasis is a critical aspect of cardiovascular health, and disruption of this balance can contribute to the development and progression of atherosclerosis. Recent studies have demonstrated that H2S plays an important role in maintaining oxygen homeostasis by regulating the function of oxygen-sensing enzymes and transcription factors in vascular cells. H2S has been shown to modulate endothelial nitric oxide synthase (eNOS) activity, which plays a key role in regulating vascular tone and oxygen delivery to tissues. The comprehensive analysis of the current understanding of H2S in atherosclerosis can pave the way for future research and the development of new therapeutic strategies for this debilitating condition. PROSPERO ID: 417150.

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Hydrogen sulfide: A new therapeutic target in vascular diseases

Cited by 16 publications

References 119 publications

Circulating Levels of Hydrogen Sulfide (H2S) in Patients with Age-Related Diseases: A Systematic Review and Meta-Analysis

Circulating Levels of Hydrogen Sulfide (H2S) in Patients with Age-Related Diseases: A Systematic Review and Meta-Analysis

Effect of Hydrogen Sulfide on Essential Functions of Polymorphonuclear Leukocytes

Hydrogen Sulfide and Oxygen Homeostasis in Atherosclerosis: A Systematic Review from Molecular Biology to Therapeutic Perspectives

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