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  • Review Article
  • Published:

Sulfide regulation of cardiovascular function in health and disease

Nature Reviews Cardiology volume 20, pages 109–125 (2023)Cite this article

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Abstract

Hydrogen sulfide (H2S) has emerged as a gaseous signalling molecule with crucial implications for cardiovascular health. H2S 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 H2S 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 H2S and its metabolites, such as hydropersulfides and polysulfides, is substantially reduced in cardiovascular disease and has been associated with single-nucleotide polymorphisms in H2S synthesis enzymes. In this Review, we highlight the role of H2S, 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.

Key points

  • Hydrogen sulfide (H2S) has a crucial role in regulating cardiovascular function; reduced bioavailability is associated with cardiovascular pathologies, including arrhythmias, heart failure, ischaemic myocardial dysfunction and peripheral vascular disease.

  • H2S and its synthesizing enzymes, including cystathionine γ-lyase, can protect against atherosclerosis and cardiac ischaemia–reperfusion injury.

  • H2S regulates various pathophysiological functions via interaction with nitric oxide, activation of molecular signalling cascades, post-translational modification of proteins and control of redox-dependent responses.

  • Findings from clinical studies demonstrate that H2S and its metabolites, including hydropersulfides and polysulfides, have substantial therapeutic potential for various forms of cardiovascular disease.

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Fig. 1: Sulfide metabolite formation and fate.
Fig. 2: Sulfide signalling and chemical reaction pathways.
Fig. 3: Sulfide regulation of cardiovascular responses involving CTH expression and function.

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Acknowledgements

The authors are supported by an LSUHSC-S CCDS COVID-19 Research Award and CoBRE Pilot Grant Award to G.K.K; an LSUHSC-S CCDS COVID-19 Research Award and CoBRE Project Grant Award to P.D.; and an Institutional Development Award (IDeA) from the National Institutes of General Medical Sciences of the NIH under grant number GM121307 and HL149264 from the National Heart, Lung, and Blood Institute of the NIH to C.G.K.

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  1. Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA, USA

    Gopi K. Kolluru, Rodney E. Shackelford, Xinggui Shen & Christopher G. Kevil

  2. Center of Excellence for Cardiovascular Diseases & Sciences, Louisiana State University Health Sciences Center, Shreveport, LA, USA

    Gopi K. Kolluru, Xinggui Shen, Paari Dominic & Christopher G. Kevil

  3. Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, LA, USA

    Paari Dominic

  4. Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, USA

    Paari Dominic & Christopher G. Kevil

  5. Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, LA, USA

    Christopher G. Kevil

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Kolluru, G.K., Shackelford, R.E., Shen, X. et al. Sulfide regulation of cardiovascular function in health and disease. Nat Rev Cardiol 20, 109–125 (2023). https://doi.org/10.1038/s41569-022-00741-6

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