Hydropersulfides promote angiogenesis and preserve vascular function

Hydropersulfides (RSSH) are increasingly recognized as key mediators in redox signalling in mammalian cells, although their physiological functions, especially in angiogenesis, remain unknown. Direct mechanistic investigation of RSSH has been challenging due to their instability and high reactivity. To address this, donors that release RSSH in a controlled manner have been developed, enabling investigation of its biological roles. Herein, we employed thiol- and enzyme-activated RSSH donors along with mutant mouse models deficient in the Cys-SSH-producing enzyme cysteinyl-tRNA synthetase/cysteine persulfide synthase (CARS2/CPERS), to examine their role in vascular angiogenesis. We demonstrate that RSSH promotes angiogenesis via the CARS2/CPERS signalling axis and activation of the Akt-eNOS and NO-cGMP pathway. We also demonstrate that nitric oxide (NO) signalling in resistance vessels requires an intact CARS2/CPER2 pathway. These findings suggest that RSSH plays an important role in regulating angiogenesis and vascular tone.

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Publication Details

Journal
Redox Biology
Published
2026-05-01
DOI
https://doi.org/10.1016/j.redox.2026.104192
Primary Topic
Sulfur Compounds in Biology
Type
article
Field-Weighted Citation Impact
0.00

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article

Hydropersulfides promote angiogenesis and preserve vascular function

Kayleigh Griffiths, Reece J. Lamb, Tsuyoshi Takata, John P. Toscano et al.
Redox Biology
Sulfur Compounds in Biology
article

Hydropersulfides promote angiogenesis and preserve vascular function

Kayleigh Griffiths, Reece J. Lamb, Tsuyoshi Takata, John P. Toscano, Jinjing Gu, Melanie Madhani, Masanobu Morita, Hozumi Motohashi, Aisah A. Aubdool, Roger J. Grand, Takaaki Akaike, Alice J. Barton, Tetsuro Matsunaga, Scott P. Davies, Ming Xian, Fifi S. Ibrahim, Vinayak S. Khodade, Francesca M. Nichols
article en

Abstract

Hydropersulfides (RSSH) are increasingly recognized as key mediators in redox signalling in mammalian cells, although their physiological functions, especially in angiogenesis, remain unknown. Direct mechanistic investigation of RSSH has been challenging due to their instability and high reactivity. To address this, donors that release RSSH in a controlled manner have been developed, enabling investigation of its biological roles. Herein, we employed thiol- and enzyme-activated RSSH donors along with mutant mouse models deficient in the Cys-SSH-producing enzyme cysteinyl-tRNA synthetase/cysteine persulfide synthase (CARS2/CPERS), to examine their role in vascular angiogenesis. We demonstrate that RSSH promotes angiogenesis via the CARS2/CPERS signalling axis and activation of the Akt-eNOS and NO-cGMP pathway. We also demonstrate that nitric oxide (NO) signalling in resistance vessels requires an intact CARS2/CPER2 pathway. These findings suggest that RSSH plays an important role in regulating angiogenesis and vascular tone.

Redox BiologyVol. 94
Johns Hopkins University (US), Queen Mary University of London (GB), Tohoku University (JP), Brown University (US), Johns Hopkins Medicine (US), Institut thématique Immunologie, inflammation, infectiologie et microbiologie (FR), National University Heart Centre Singapore (SG), National Heart Centre Singapore (SG), William Harvey Research Institute (GB), Centre for Inflammation Research (GB), University of Birmingham (GB)
National Science Foundation, British Heart Foundation
Zero hunger
Openalex Percentile: Top 11%
Sulfur Compounds in Biology
DOIOpen Access PDFOpenAlex
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