The Drug Developments of Hydrogen Sulfide on Cardiovascular Disease

Wen, Yujie; Wang, Hong; Zhu, Yi‐Zhun

doi:10.1155/2018/4010395

Cited by 73 publications

(69 citation statements)

References 177 publications

(239 reference statements)

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“…These conflicting results imply that H 2 S acts as a pivotal regulator of leukocyte activation under different inflammatory states. However, in recent years, more studies support that H 2 S could inhibit the process of endothelial cell inflammation (Wen et al, 2018). For instance, specific endothelial deletion of CSE is associated with the development of endothelial inflammation and atherosclerosis, effects that are reversed on treatment with a polysulfide donor (Bibli et al, 2019).…”

Section: Role Of H 2 S In Endothelial Inflammationmentioning

confidence: 99%

Role of Endothelial Dysfunction in Cardiovascular Diseases: The Link Between Inflammation and Hydrogen Sulfide

et al. 2020

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Endothelial cells are important constituents of blood vessels that play critical roles in cardiovascular homeostasis by regulating blood fluidity and fibrinolysis, vascular tone, angiogenesis, monocyte/leukocyte adhesion, and platelet aggregation. The normal vascular endothelium is taken as a gatekeeper of cardiovascular health, whereas abnormality of vascular endothelium is a major contributor to a plethora of cardiovascular ailments, such as atherosclerosis, aging, hypertension, obesity, and diabetes. Endothelial dysfunction is characterized by imbalanced vasodilation and vasoconstriction, elevated reactive oxygen species (ROS), and proinflammatory factors, as well as deficiency of nitric oxide (NO) bioavailability. The occurrence of endothelial dysfunction disrupts the endothelial barrier permeability that is a part of inflammatory response in the development of cardiovascular diseases. As such, abrogation of endothelial cell activation/inflammation is of clinical relevance. Recently, hydrogen sulfide (H 2 S), an entry as a gasotransmitter, exerts diverse biological effects through acting on various targeted signaling pathways. Within the cardiovascular system, the formation of H 2 S is detected in smooth muscle cells, vascular endothelial cells, and cardiomyocytes. Disrupted H 2 S bioavailability is postulated to be a new indicator for endothelial cell inflammation and its associated endothelial dysfunction. In this review, we will summarize recent advances about the roles of H 2 S in endothelial cell homeostasis, especially under pathological conditions, and discuss its putative therapeutic applications in endothelial inflammation-associated cardiovascular disorders.

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Section: Role Of H 2 S In Endothelial Inflammationmentioning

confidence: 99%

Role of Endothelial Dysfunction in Cardiovascular Diseases: The Link Between Inflammation and Hydrogen Sulfide

et al. 2020

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“…A. baumannii is a critically important AMR pathogen for which therapeutic options are increasingly limited with isolates now displaying resistance to last resort drug including colistin. H2S-releasing molecules have been developed for a wide range of clinical applications (Gemici et al, 2015;Wen et al, 2018). Their ability to increase H2S concentration in several body compartments, along with their safety profile, have been reported (Toombs et al, 2010;Wallace, 2015;Wallace et al, 2020).…”

Section: Membrane Permeability Remained Unchanged (Supplementarymentioning

confidence: 99%

Hydrogen Sulfide Sensitizes Acinetobacter baumannii to Killing by Antibiotics

Ong

Surendran

et al. 2020

Front. Microbiol.

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The production of endogenous hydrogen sulfide (H 2 S) has been shown to confer antibiotic tolerance in all bacteria studied to date. Therefore, this mediator has been speculated to be a universal defense mechanism against antibiotics in bacteria. This is assuming that all bacteria produce endogenous H 2 S. In this study, we established that the pathogenic bacteria Acinetobacter baumannii does not produce endogenous H 2 S, giving us the opportunity to test the effect of exogenous H 2 S on antibiotic tolerance in a bacterium that does not produce it. By using a H 2 S-releasing compound to modulate the sulfide content in A. baumannii, we demonstrated that instead of conferring antibiotic tolerance, exogenous H 2 S sensitized A. baumannii to multiple antibiotic classes, and was able to revert acquired resistance to gentamicin. Exogenous H 2 S triggered a perturbation of redox and energy homeostasis that translated into hypersensitivity to antibiotic killing. We propose that H 2 S could be used as an antibiotic-potentiator and resistance-reversion agent in bacteria that do not produce it.

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“…S-memantine exerts lower toxicity and greater therapeutic effects against cerebral ischemic injury in vitro and in vivo than do H 2 S-releasing molecule alone or sulfide salt [60]. Some of H 2 S-releasing compounds have been tested in clinical trials [67][68][69]. Wallace and colleagues showed in a phase 2B clinical trial that naproxen chemically conjugated with a H 2 S-releasing moiety, ATB-346, inhibits COX-2 as well as naproxen with less gastrointestinal damage than naproxen (ClinicalTrials.gov Identifier: NCT03978208, NCT03291418) [67].…”

Section: Administration Of H 2 S Donor As Therapeutic Measurementioning

confidence: 99%

Emerging pharmacological tools to control hydrogen sulfide signaling in critical illness

Marutani

Ichinose

2020

ICMx

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Hydrogen sulfide (H 2 S) has long been known as a toxic environmental hazard. Discovery of physiological roles of H 2 S as a neurotransmitter by Kimura and colleagues triggered an intensive research in the biological roles of H 2 S in the past decades. Manipulation of H 2 S levels by inhibiting H 2 S synthesis or administration of H 2 S-releasing molecules revealed beneficial as well as harmful effects of H 2 S. As a result, it is now established that H 2 S levels are tightly controlled and too much or too little H 2 S levels cause harm. Nonetheless, translation of sulfide-based therapy to clinical practice has been stymied due to the very low therapeutic index of sulfide and the incomplete understanding of endogenous sulfide metabolism. One potential strategy to circumvent this problem is to use a safe and stable sulfide metabolite that may mediate effects of H 2 S. Alternatively, endogenous sulfide levels may be controlled using specific sulfide scavengers. In this review article, the role of endogenous H 2 S production and catabolism will be briefly reviewed followed by an introduction of thiosulfate and H 2 S scavengers as novel pharmacological tools to control H 2 S-dependent signaling.

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The Drug Developments of Hydrogen Sulfide on Cardiovascular Disease

Cited by 73 publications

References 177 publications

Role of Endothelial Dysfunction in Cardiovascular Diseases: The Link Between Inflammation and Hydrogen Sulfide

Role of Endothelial Dysfunction in Cardiovascular Diseases: The Link Between Inflammation and Hydrogen Sulfide

Hydrogen Sulfide Sensitizes Acinetobacter baumannii to Killing by Antibiotics

Emerging pharmacological tools to control hydrogen sulfide signaling in critical illness

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