Hydrogen Sulfide as a Potential Therapy for Heart Failure—Past, Present, and Future

LaPenna, Kyle B.; Polhemus, David J.; Doiron, Jake E.; Hidalgo, Hunter; Li, Zhen; Lefer, David J.

doi:10.3390/antiox10030485

Cited by 22 publications

(17 citation statements)

References 76 publications

(97 reference statements)

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“…The current literature clearly demonstrates that H 2 S is an important independent effector 8 – 11 , as well as an enhancer of NO-mediated signalling events affecting the cardiovascular system 12 – 14 . A cardioprotective role for H 2 S has been suggested in cardiac arrhythmias, cardiac fibrosis, heart failure, cardiac hypertrophy, ischaemia–reperfusion injury (IRI) and myocardial infarction (MI) 10 . Although the role of H 2 S and its metabolites as biomarkers of human cardiovascular disease (CVD) is not yet well established 15 , improved detection techniques have identified novel sulfide metabolites, including hydropersulfides and polysulfides, and have begun to reveal previously unknown molecular mechanisms and their biological relevance in cardiovascular pathology.…”

Section: Introductionmentioning

confidence: 99%

Sulfide regulation of cardiovascular function in health and disease

et al. 2022

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Hydrogen sulfide (H 2 S) has emerged as a gaseous signalling molecule with crucial implications for cardiovascular health. H 2 S is involved in many biological functions, including interactions with nitric oxide, activation of molecular signalling cascades, post-translational modifications and redox regulation. Various preclinical and clinical studies have shown that H 2 S and its synthesizing enzymes — cystathionine γ-lyase, cystathionine β-synthase and 3-mercaptosulfotransferase — can protect against cardiovascular pathologies, including arrhythmias, atherosclerosis, heart failure, myocardial infarction and ischaemia–reperfusion injury. The bioavailability of H 2 S and its metabolites, such as hydropersulfides and polysulfides, is substantially reduced in cardiovascular disease and has been associated with single-nucleotide polymorphisms in H 2 S synthesis enzymes. In this Review, we highlight the role of H 2 S, its synthesizing enzymes and metabolites, their roles in the cardiovascular system, and their involvement in cardiovascular disease and associated pathologies. We also discuss the latest clinical findings from the field and outline areas for future study.

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Section: Introductionmentioning

confidence: 99%

Sulfide regulation of cardiovascular function in health and disease

et al. 2022

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“…There are many pharmacological avenues to achieve this latter goal; H 2 S donors with various release rates have been designed and tested, some of them organelle-targeted, some redox-triggered. These molecules are subject to focused review articles [ 5 , 58 – 64 ]. Unfortunately, these approaches are currently only in the preclinical stage, with the notable exception of SG-1002, which is a clinical-stage molecule, and which exhibits protective effects in various preclinical models of aging-associated diseases including atherosclerosis, chronic heart failure, and diet-induced obesity [ 61 , 65 – 68 ].…”

Section: Perspectivesmentioning

confidence: 99%

Inhibition of the 3-mercaptopyruvate sulfurtransferase—hydrogen sulfide system promotes cellular lipid accumulation

et al. 2022

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H2S is generated in the adipose tissue by cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase (3-MST). H2S plays multiple roles in the regulation of various metabolic processes, including insulin resistance. H2S biosynthesis also occurs in adipocytes. Aging is known to be associated with a decline in H2S. Therefore, the question arises whether endogenous H2S deficiency may affect the process of adipocyte maturation and lipid accumulation. Among the three H2S-generating enzymes, the role of 3-MST is the least understood in adipocytes. Here we tested the effect of the 3-MST inhibitor 2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one (HMPSNE) and the H2S donor (GYY4137) on the differentiation and adipogenesis of the adipocyte-like cells 3T3-L1 in vitro. 3T3-L1 cells were differentiated into mature adipocytes in the presence of GYY4137 or HMPSNE. HMPSNE significantly enhanced lipid accumulation into the maturing adipocytes. On the other hand, suppressed lipid accumulation was observed in cells treated with the H2S donor. 3-MST inhibition increased, while H2S donation suppressed the expression of various H2S-producing enzymes during adipocyte differentiation. 3-MST knockdown also facilitated adipocytic differentiation and lipid uptake. The underlying mechanisms may involve impairment of oxidative phosphorylation and fatty acid oxidation as well as the activation of various differentiation-associated transcription factors. Thus, the 3-MST/H2S system plays a tonic role in suppressing lipid accumulation and limiting the differentiation of adipocytes. Stimulation of 3-MST activity or supplementation of H2S—which has been recently linked to various experimental therapeutic approaches during aging—may be a potential experimental approach to counteract adipogenesis.

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“…3-MST is more abundant in cardiomyocytes and smooth muscle than CSE and, curiously, deletion of 3-MST protects young mice from reperfusion injury but exacerbates in in older 3-MST -/- mice and predisposes them to hypertension and cardiac hypertrophy [ 155 ]. Additional information can be found in recent reviews [ 156 , 157 , 158 ].…”

Section: Evidence For H 2 S Mediated O 2 Sensing In Various Organ Systems and Tissuesmentioning

confidence: 99%

A Case for Hydrogen Sulfide Metabolism as an Oxygen Sensing Mechanism

Olson

2021

Antioxidants

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The ability to detect oxygen availability is a ubiquitous attribute of aerobic organisms. However, the mechanism(s) that transduce oxygen concentration or availability into appropriate physiological responses is less clear and often controversial. This review will make the case for oxygen-dependent metabolism of hydrogen sulfide (H2S) and polysulfides, collectively referred to as reactive sulfur species (RSS) as a physiologically relevant O2 sensing mechanism. This hypothesis is based on observations that H2S and RSS metabolism is inversely correlated with O2 tension, exogenous H2S elicits physiological responses identical to those produced by hypoxia, factors that affect H2S production or catabolism also affect tissue responses to hypoxia, and that RSS efficiently regulate downstream effectors of the hypoxic response in a manner consistent with a decrease in O2. H2S-mediated O2 sensing is then compared to the more generally accepted reactive oxygen species (ROS) mediated O2 sensing mechanism and a number of reasons are offered to resolve some of the confusion between the two.

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Hydrogen Sulfide as a Potential Therapy for Heart Failure—Past, Present, and Future

Cited by 22 publications

References 76 publications

Sulfide regulation of cardiovascular function in health and disease

Sulfide regulation of cardiovascular function in health and disease

Inhibition of the 3-mercaptopyruvate sulfurtransferase—hydrogen sulfide system promotes cellular lipid accumulation

A Case for Hydrogen Sulfide Metabolism as an Oxygen Sensing Mechanism

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