{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:31Z","timestamp":1787028571546,"version":"build-2736575974"},"reference-count":121,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)","doi-asserted-by":"publisher","award":["RS-2025-02216513"],"award-info":[{"award-number":["RS-2025-02216513"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chungnam National University","award":["RS-2025-02216513"],"award-info":[{"award-number":["RS-2025-02216513"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hydrogen sulfide (H2S), nitric oxide (NO), and carbon monoxide (CO) are now recognized as key gasotranmitters that regulate vascular function, contributing to vasodilation, angiogenesis, inflammation control, and oxidative balance. Initially regarded as toxic gases, they are produced on demand by specific enzymes, including cystathionine \u03b3-lyase (CSE), endothelial nitric oxide synthase (eNOS), and heme oxygenase-1 (HO-1). Their activity is tightly controlled by redox-sensitive pathways. Reactive oxygen species (ROS), particularly superoxide and hydrogen peroxide, modulate gasotransmitter biosynthesis at the transcriptional and post-translational levels. Moreover, ROS affect gasotransmitter availability through oxidative modifications, including thiol persulfidation, nitrosative signaling, and carbonylation. This redox regulation ensures a tightly coordinated response to environmental and metabolic cues within the vascular system. This review synthesizes the current understanding of redox\u2013gasotransmitter interactions, highlighting how ROS modulate the vascular roles of H2S, NO, and CO. Understanding these interactions provides critical insights into the pathogenesis of cardiovascular diseases and offers potential redox-targeted therapies.<\/jats:p>","DOI":"10.3390\/ijms26189037","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T08:03:47Z","timestamp":1758096227000},"page":"9037","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Redox Regulation of Endogenous Gasotransmitters in Vascular Health and Disease"],"prefix":"10.3390","volume":"26","author":[{"given":"Giang-Huong","family":"Vu","sequence":"first","affiliation":[{"name":"Department of Physiology & Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7647-6089","authenticated-orcid":false,"given":"Cuk-Seong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology & Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1089\/ars.2011.4349","article-title":"Role of Cystathionine \u03b3-Lyase\/Hydrogen Sulfide Pathway in Cardiovascular Disease: A Novel Therapeutic Strategy?","volume":"17","author":"Pan","year":"2012","journal-title":"Antioxid. Redox Signal"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1093\/cvr\/cvq139","article-title":"The NO cascade, eNOS location, and microvascular permeability","volume":"87","author":"Breslin","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ryter, S.W. (2022). Heme Oxygenase-1: An Anti-Inflammatory Effector in Cardiovascular, Lung, and Related Metabolic Disorders. Antioxidants, 11.","DOI":"10.3390\/antiox11030555"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Arrigo, E., Comita, S., Pagliaro, P., Penna, C., and Mancardi, D. (2023). Clinical Applications for Gasotransmitters in the Cardiovascular System: Are We There Yet?. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512480"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1097\/00004872-200310000-00015","article-title":"The role of hydrogen sulfide generation in the pathogenesis of hypertension in rats induced by inhibition of nitric oxide synthase","volume":"21","author":"Zhong","year":"2003","journal-title":"J. Hypertens."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1161\/CIRCULATIONAHA.112.000855","article-title":"H2S Protects Against Pressure Overload-Induced Heart Failure via Upregulation of Endothelial Nitric Oxide Synthase","volume":"127","author":"Kondo","year":"2013","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3133","DOI":"10.2174\/138161209789058002","article-title":"Prevention of Atherosclerosis by Interference with the Vascular Nitric Oxide System","volume":"15","author":"Li","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1089\/ars.2005.7.704","article-title":"Carbon monoxide signaling in promoting angiogenesis in human microvessel endothelial cells","volume":"7","author":"Volti","year":"2005","journal-title":"Antioxid. Redox Signal"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1161\/CIRCRESAHA.112.268680","article-title":"Cysteine Oxidative Posttranslational Modifications Emerging Regulation in the Cardiovascular System","volume":"112","author":"Chung","year":"2013","journal-title":"Circ. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1126\/science.1144318","article-title":"Cysteine redox sensor in PKGI\u03b1 enables oxidant-induced activation","volume":"317","author":"Burgoyne","year":"2007","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1007\/s00204-024-03751-0","article-title":"Vascular endothelial dysfunction induced by 3-bromofluoranthene via MAPK-mediated-NF\u03baB pro-inflammatory pathway and intracellular ROS generation","volume":"98","author":"Lee","year":"2024","journal-title":"Arch. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1124\/jpet.119.262048","article-title":"Impaired Endothelium-Dependent Hyperpolarization Underlies Endothelial Dysfunction during Early Metabolic Challenge: Increased ROS Generation and Possible Interference with NO Function","volume":"371","author":"Alaaeddine","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1161\/HYPERTENSIONAHA.114.04760","article-title":"Activation of Nuclear Factor Erythroid 2-Related Factor 2 Coordinates Dimethylarginine Dimethylaminohydrolase\/PPAR-\u03b3\/Endothelial Nitric Oxide Synthase Pathways That Enhance Nitric Oxide Generation in Human Glomerular Endothelial Cells","volume":"65","author":"Luo","year":"2015","journal-title":"Hypertension"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1096\/fj.14-266015","article-title":"Proresolution effects of hydrogen sulfide during colitis are mediated through hypoxia-inducible factor-1\u03b1","volume":"29","author":"Flannigan","year":"2015","journal-title":"Faseb J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1089\/ars.2020.8132","article-title":"Are Reactive Sulfur Species the New Reactive Oxygen Species?","volume":"33","author":"Olson","year":"2020","journal-title":"Antioxid. Redox Signal"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1089\/152308601300185179","article-title":"Mechanisms of the antioxidant effects of nitric oxide","volume":"3","author":"Wink","year":"2001","journal-title":"Antioxid. Redox Signal"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1111\/bph.13828","article-title":"Reactive oxygen species: Key regulators in vascular health and diseases","volume":"175","author":"Chen","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ciccone, V., Genah, S., and Morbidelli, L. (2021). Endothelium as a Source and Target of H2S to Improve Its Trophism and Function. Antioxidants, 10.","DOI":"10.3390\/antiox10030486"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Choi, Y.K., and Kim, Y.M. (2021). Regulation of Endothelial and Vascular Functions by Carbon Monoxide via Crosstalk With Nitric Oxide. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.649630"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.freeradbiomed.2017.04.025","article-title":"Redox regulation of gasotransmission in the vascular system: A focus on angiogenesis","volume":"108","author":"Mistry","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.mito.2021.11.002","article-title":"Targeting the redox imbalance in mitochondria: A novel mode for cancer therapy","volume":"62","author":"Mani","year":"2022","journal-title":"Mitochondrion"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3281","DOI":"10.1007\/s00018-015-1928-9","article-title":"ROS signaling and redox biology in endothelial cells","volume":"72","author":"Panieri","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1093\/aob\/mcf118","article-title":"Antioxidants, oxidative damage and oxygen deprivation stress: A review","volume":"91","author":"Blokhina","year":"2003","journal-title":"Ann. Bot."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1089\/ars.2007.1556","article-title":"VEGF signaling through NADPH oxidase-derived ROS","volume":"9","year":"2007","journal-title":"Antioxid. Redox Signal"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Garrido-Urbani, S., Jemelin, S., Deffert, C., Carnesecchi, S., Basset, O., Szyndralewiez, C., Heitz, F., Page, P., Montet, X., and Michalik, L. (2011). Targeting Vascular NADPH Oxidase 1 Blocks Tumor Angiogenesis through a PPAR\u03b1 Mediated Mechanism. PLoS ONE, 6.","DOI":"10.1371\/annotation\/a392bbef-b0ec-4c70-b403-74a7bad85178"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1113\/jphysiol.2014.284901","article-title":"Nox4 supports proper capillary growth in exercise and retina neo-vascularization","volume":"593","author":"Vogel","year":"2015","journal-title":"J. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Chen, W., Xiang, H., Chen, R.F., Yang, J., Yang, X.P., Zhou, J.D., Liu, H.D., Zhao, S.L., Xiao, J., and Chen, P. (2019). S1PR2 antagonist ameliorate high glucose-induced fission and dysfunction of mitochondria in HRGECs via regulating ROCK1. BMC Nephrol., 20.","DOI":"10.1186\/s12882-019-1323-0"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41420-024-02278-8","article-title":"Free radicals and their impact on health and antioxidant defenses: A review","volume":"11","author":"Chandimali","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Munteanu, C., Galaction, A.I., Onose, G., Turnea, M., and Rotariu, M. (2025). Harnessing Gasotransmitters to Combat Age-Related Oxidative Stress in Smooth Muscle and Endothelial Cells. Pharmaceuticals, 18.","DOI":"10.3390\/ph18030344"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.plaphy.2020.09.020","article-title":"Hydrogen sulfide regulates the activity of antioxidant enzymes through persulfidation and improves the resistance of tomato seedling to Copper Oxide nanoparticles (CuO NPs)-induced oxidative stress","volume":"156","author":"Li","year":"2020","journal-title":"Plant Physiol. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"H1781","DOI":"10.1152\/ajpheart.00930.2008","article-title":"Superoxide-mediated inactivation of nitric oxide and peroxynitrite formation by tobacco smoke in vascular endothelium: Studies in cultured cells and smokers","volume":"296","author":"Peluffo","year":"2009","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Benchoam, D., Cuevasanta, E., M\u00f6ller, M.N., and Alvarez, B. (2019). Hydrogen Sulfide and Persulfides Oxidation by Biologically Relevant Oxidizing Species. Antioxidants, 8.","DOI":"10.3390\/antiox8020048"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"794237","DOI":"10.1155\/2012\/794237","article-title":"Regulation of ROS Production and Vascular Function by Carbon Monoxide","volume":"2012","author":"Choi","year":"2012","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1111\/bph.14446","article-title":"Regulators of the transsulfuration pathway","volume":"176","author":"Sbodio","year":"2019","journal-title":"Br. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1152\/physrev.00028.2021","article-title":"Physiological Roles of Hydrogen Sulfide in Mammalian Cells, Tissues, and Organs","volume":"103","author":"Cirino","year":"2023","journal-title":"Physiol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Janaszak-Jasiecka, A., Ploska, A., Wieronska, J.M., Dobrucki, L.W., and Kalinowski, L. (2023). Endothelial dysfunction due to eNOS uncoupling: Molecular mechanisms as potential therapeutic targets. Cell. Mol. Biol. Lett., 28.","DOI":"10.1186\/s11658-023-00423-2"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1016\/j.bbagen.2015.09.018","article-title":"Ferritin heavy chain mediates the protective effect of heme oxygenase-1 against oxidative stress","volume":"1850","author":"Cheng","year":"2015","journal-title":"BBA-Gen. Subj."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ab.2005.03.024","article-title":"Polarographic measurement of hydrogen sulfide production and consumption by mammalian tissues","volume":"341","author":"Doeller","year":"2005","journal-title":"Anal. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"52082","DOI":"10.1074\/jbc.C400481200","article-title":"Production of the neuromodulator H2S by cystathionine \u03b2-synthase via the condensation of cysteine and homocysteine","volume":"279","author":"Chen","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.niox.2013.07.002","article-title":"Hydrogen sulfide chemical biology: Pathophysiological roles and detection","volume":"35","author":"Kolluru","year":"2013","journal-title":"Nitric Oxide-Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1093\/jb\/mvr018","article-title":"Production of H2S by 3-mercaptopyruvate sulphurtransferase","volume":"149","author":"Tanizawa","year":"2011","journal-title":"J. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"22457","DOI":"10.1074\/jbc.M109.010868","article-title":"Relative Contributions of Cystathionine \u03b2-Synthase and \u03b3-Cystathionase to H2S Biogenesis via Alternative Trans-sulfuration Reactions","volume":"284","author":"Singh","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1093\/jb\/mvp111","article-title":"Vascular Endothelium Expresses 3-Mercaptopyruvate Sulfurtransferase and Produces Hydrogen Sulfide","volume":"146","author":"Shibuya","year":"2009","journal-title":"J. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1016\/j.bbrc.2005.10.118","article-title":"Cystathionine \u03b2-synthase is enriched in the brains of Down\u2019s patients","volume":"338","author":"Ichinohe","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1096\/fj.05-3724fje","article-title":"Cystathionine \u03b2-synthase, a key enzyme for homocysteine metabolism, is preferentially expressed in the radial glia\/astrocyte lineage of developing mouse CNS","volume":"19","author":"Enokido","year":"2005","journal-title":"Faseb J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1089\/ars.2008.2253","article-title":"3-Mercaptopyruvate Sulfurtransferase Produces Hydrogen Sulfide and Bound Sulfane Sulfur in the Brain","volume":"11","author":"Shibuya","year":"2009","journal-title":"Antioxid. Redox Signal"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1097\/HJH.0000000000002101","article-title":"Hydrogen sulfide improves endothelial dysfunction by inhibiting the vicious cycle of NLRP3 inflammasome and oxidative stress in spontaneously hypertensive rats","volume":"37","author":"Li","year":"2019","journal-title":"J. Hypertens."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"H1446","DOI":"10.1152\/ajpheart.00506.2012","article-title":"Hydrogen sulfide dilates rat mesenteric arteries by activating endothelial large-conductance Ca-activated K channels and smooth muscle Ca sparks","volume":"304","author":"Osmond","year":"2013","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.cardiores.2007.05.026","article-title":"The novel proangiogenic effect of hydrogen sulfide is dependent on Akt phosphorylation","volume":"76","author":"Cai","year":"2007","journal-title":"Cardiovasc. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"H1437","DOI":"10.1152\/ajpheart.00465.2016","article-title":"Hydrogen sulfide-induced vasodilation mediated by endothelial TRPV4 channels","volume":"311","author":"Naik","year":"2016","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.2337\/db16-0020","article-title":"Hydrogen Sulfide Induces Keap1 S-sulfhydration and Suppresses Diabetes-Accelerated Atherosclerosis via Nrf2 Activation","volume":"65","author":"Xie","year":"2016","journal-title":"Diabetes"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"235","DOI":"10.3727\/105221613X13571653093286","article-title":"Cystathionine Gamma-Lyase Expression Is Regulated by Exogenous Hydrogen Peroxide in the Mammalian Cells","volume":"15","author":"Wang","year":"2012","journal-title":"Gene Expr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1074\/jbc.M115.685578","article-title":"Transcriptional Regulation of Cystathionine-\u03b3-Lyase in Endothelial Cells by NADPH Oxidase 4-Dependent Signaling","volume":"291","author":"Mistry","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1089\/ars.2012.5041","article-title":"Polysulfides Link H2S to Protein Thiol Oxidation","volume":"19","author":"Greiner","year":"2013","journal-title":"Antioxid. Redox Signal"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"E517","DOI":"10.1161\/CIRCULATIONAHA.114.010273","article-title":"Response to Letter Regarding Article, \u201cDysregulation of Hydrogen Sulfide (H2S) Producing Enzyme Cystathionine \u03b3-lyase (CSE) Contributes to Maternal Hypertension and Placental Abnormalities in Preeclampsia\u201d","volume":"129","author":"Wang","year":"2014","journal-title":"Circulation"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1161\/HYPERTENSIONAHA.117.10562","article-title":"Cystathionine \u03b3-Lyase Produced Hydrogen Sulfide Controls Endothelial NO Bioavailability and Blood Pressure","volume":"71","author":"Filipovic","year":"2018","journal-title":"Hypertension"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e017544","DOI":"10.1161\/JAHA.120.017544","article-title":"Endothelial Cell Cystathionine \u03b3-Lyase Expression Level Modulates Exercise Capacity, Vascular Function, and Myocardial Ischemia Reperfusion Injury","volume":"9","author":"Xia","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e14021","DOI":"10.1111\/apha.14021","article-title":"Inhibition of cystathionine-gamma lyase dampens vasoconstriction in mouse and human intracerebral arterioles","volume":"239","author":"Peleli","year":"2023","journal-title":"Acta Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.neuint.2006.09.014","article-title":"Inhibition of cystathionine-\u03b3-lyase leads to loss of glutathione and aggravation of mitochondrial dysfunction mediated by excitatory amino acid in the CNS","volume":"50","author":"Diwakar","year":"2007","journal-title":"Neurochem. Int."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"503","DOI":"10.2119\/molmed.2013.00096","article-title":"Hydrogen Sulfide Alleviates Myocardial Collagen Remodeling in Association with Inhibition of TGF-\u03b2\/Smad Signaling Pathway in Spontaneously Hypertensive Rats","volume":"20","author":"Sun","year":"2014","journal-title":"Mol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1291\/hypres.31.1619","article-title":"Regulatory Effect of Hydrogen Sulfide on Vascular Collagen Content in Spontaneously Hypertensive Rats","volume":"31","author":"Zhao","year":"2008","journal-title":"Hypertens. Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ciccone, V., Piragine, E., Gorica, E., Citi, V., Testai, L., Pagnotta, E., Matteo, R., Pecchioni, N., Montanaro, R., and Mannelli, L.D. (2022). Anti-Inflammatory Effect of the Natural H2S-Donor Erucin in Vascular Endothelium. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415593"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.ccc.2019.12.009","article-title":"Nitric Oxide and Endothelial Dysfunction","volume":"36","author":"Cyr","year":"2020","journal-title":"Crit. Care Clin."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/S0005-2728(99)00024-9","article-title":"Guanylate cyclase and the .NO\/cGMP signaling pathway","volume":"1411","author":"Denninger","year":"1999","journal-title":"Biochim. Biophys. Acta-Bioenerg."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s00726-006-0427-6","article-title":"Regulation of apoptosis by protein S-nitrosylation","volume":"32","author":"Mannick","year":"2007","journal-title":"Amino Acids"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4810","DOI":"10.1074\/jbc.M112.426353","article-title":"Nitric-oxide Synthase-2 Linkage to Focal Adhesion Kinase in Neutrophils Influences Enzyme Activity and \u03b22 Integrin Function","volume":"288","author":"Thom","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Matrullo, G., Filomeni, G., and Rizza, S. (2025). Redox regulation of focal adhesions. Redox Biol., 80.","DOI":"10.1016\/j.redox.2025.103514"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3823","DOI":"10.1016\/j.neuron.2024.10.013","article-title":"Redox regulation, protein S-nitrosylation, and synapse loss in Alzheimer\u2019s and related dementias","volume":"112","author":"Oh","year":"2024","journal-title":"Neuron"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1161\/CIRCRESAHA.112.267054","article-title":"Nox4 Is a Protective Reactive Oxygen Species Generating Vascular NADPH Oxidase","volume":"110","author":"Zhang","year":"2012","journal-title":"Circ. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"26464","DOI":"10.1074\/jbc.R113.472936","article-title":"Peroxynitrite, a Stealthy Biological Oxidant","volume":"288","author":"Radi","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Torres, I., Manzano-Pech, L., Rubio-Ru\u00edz, M.E., Soto, M.E., and Guarner-Lans, V. (2020). Nitrosative Stress and Its Association with Cardiometabolic Disorders. Molecules, 25.","DOI":"10.3390\/molecules25112555"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1042\/bj3590139","article-title":"Nitric oxide inhibits mitochondrial NADH:ubiquinone reductase activity through peroxynitrite formation","volume":"359","author":"Clementi","year":"2001","journal-title":"Biochem. J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1006\/abbi.1996.0178","article-title":"Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport","volume":"328","author":"Cassina","year":"1996","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"302","DOI":"10.2174\/1874192401004010302","article-title":"The endothelium and its role in regulating vascular tone","volume":"4","author":"Sandoo","year":"2010","journal-title":"Open Cardiovasc. Med. J."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Aguilar, G., Koning, T., Ehrenfeld, P., and Sanchez, F.A. (2020). Role of NO and S-nitrosylation in the Expression of Endothelial Adhesion Proteins That Regulate Leukocyte and Tumor Cell Adhesion. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.595526"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.niox.2003.11.005","article-title":"Molecular mechanisms of nitric oxide-induced growth arrest and apoptosis in fetal pulmonary arterial smooth muscle cells","volume":"9","author":"Wedgwood","year":"2003","journal-title":"Nitric Oxide"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"16771","DOI":"10.1016\/S0021-9258(18)41847-9","article-title":"Nitric-Oxide Causes Adp-Ribosylation and Inhibition of Glyceraldehyde-3-Phosphate Dehydrogenase","volume":"267","author":"Dimmeler","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.4049\/jimmunol.140.8.2829","article-title":"Differentiation of murine macrophages to express nonspecific cytotoxicity for tumor cells results in L-arginine-dependent inhibition of mitochondrial iron-sulfur enzymes in the macrophage effector cells","volume":"140","author":"Drapier","year":"1988","journal-title":"J. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0891-5849(00)00512-8","article-title":"Modulation of catalase peroxidatic and catalatic activity by nitric oxide","volume":"30","author":"Brunelli","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1161\/HYPERTENSIONAHA.120.16718","article-title":"Increase in Bioavailability of Nitric Oxide After Renal Denervation Improves Kidney Function in Sheep With Hypertensive Kidney Disease","volume":"77","author":"Singh","year":"2021","journal-title":"Hypertension"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e041261","DOI":"10.1161\/JAHA.124.041261","article-title":"ELABELA Ameliorates Atherosclerosis Through Restoring the M1\/M2 Macrophage Balance in ApoE\u2212\/\u2212 Mice","volume":"14","author":"Tang","year":"2025","journal-title":"J. Am. Heart Assoc."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.redox.2017.06.002","article-title":"Dietary nitrate attenuates renal ischemia-reperfusion injuries by modulation of immune responses and reduction of oxidative stress","volume":"13","author":"Yang","year":"2017","journal-title":"Redox Biol."},{"key":"ref_83","first-page":"100175","article-title":"Exploring the medicinal significance of L-Arginine mediated nitric oxide in preventing health disorders","volume":"12","author":"Oyovwi","year":"2024","journal-title":"Eur. J. Med. Chem. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.freeradbiomed.2025.06.009","article-title":"Pharmacological targeting of endothelial nitric oxide synthase dysfunction and nitric oxide replacement therapy","volume":"237","author":"Li","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1124\/pr.57.4.3","article-title":"Carbon monoxide: Endogenous production, physiological functions, and pharmacological applications","volume":"57","author":"Wu","year":"2005","journal-title":"Pharmacol. Rev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1165\/rcmb.2009-0170TR","article-title":"Heme oxygenase-1\/carbon monoxide: From metabolism to molecular therapy","volume":"41","author":"Ryter","year":"2009","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"H1","DOI":"10.1152\/ajpheart.00230.2011","article-title":"Carbon monoxide as an endogenous vascular modulator","volume":"301","author":"Leffler","year":"2011","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.thromres.2004.04.015","article-title":"Carbon monoxide inhibits capacitative calcium entry in human platelets","volume":"114","author":"Gende","year":"2004","journal-title":"Thromb. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1111\/bph.12680","article-title":"The CO donor CORM-2 inhibits LPS-induced vascular cell adhesion molecule-1 expression and leukocyte adhesion in human rheumatoid synovial fibroblasts","volume":"171","author":"Chi","year":"2014","journal-title":"Brit J. Pharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5045","DOI":"10.1021\/jacs.3c12025","article-title":"Highly Activated Terminal Carbon Monoxide Ligand in an Iron-Sulfur Cluster Model of FeMco with Intermediate Local Spin State at Fe","volume":"146","author":"Le","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1006\/abbi.2001.2671","article-title":"The role of heme and iron-sulfur clusters in mitochondrial biogenesis, maintenance, and decay with age","volume":"397","author":"Atamna","year":"2002","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1161\/HYPERTENSIONAHA.114.04208","article-title":"Nicotinamide Adenine Dinucleotide Phosphate Oxidase-4-Dependent Upregulation of Nuclear Factor Erythroid-Derived 2-Like 2 Protects the Heart During Chronic Pressure Overload","volume":"65","author":"Smyrnias","year":"2015","journal-title":"Hypertension"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5375","DOI":"10.1074\/jbc.272.9.5375","article-title":"Hypoxia-inducible factor-1 mediates transcriptional activation of the heme oxygenase-1 gene in response to hypoxia","volume":"272","author":"Lee","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_94","first-page":"139","article-title":"An important role of Nrf2-ARE pathway in the cellular defense mechanism","volume":"37","author":"Lee","year":"2004","journal-title":"J. Biochem. Mol. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1016\/S0891-5849(00)00239-2","article-title":"Indirect inhibition of mitochondrial dihydroorotate dehydrogenase activity by nitric oxide","volume":"28","author":"Beuneu","year":"2000","journal-title":"Free Radic. Biol. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.freeradbiomed.2008.05.013","article-title":"Carbon monoxide, reactive oxygen signaling, and oxidative stress","volume":"45","author":"Piantadosi","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1161\/ATVBAHA.113.302302","article-title":"p21-Dependent Protective Effects of a Carbon Monoxide-Releasing Molecule-3 in Pulmonary Hypertension","volume":"34","author":"Abid","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1161\/01.ATV.0000142364.85911.0e","article-title":"Carbon monoxide protects against cardiac ischemia-reperfusion injury in vivo via MAPK and Akt-eNOS pathways","volume":"24","author":"Fujimoto","year":"2004","journal-title":"Arter. Throm Vas."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Lancel, S., Montaigne, D., Marechal, X., Marciniak, C., Hassoun, S.M., Decoster, B., Ballot, C., Blazejewski, C., Corseaux, D., and Lescure, B. (2012). Carbon Monoxide Improves Cardiac Function and Mitochondrial Population Quality in a Mouse Model of Metabolic Syndrome. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041836"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/S0002-9440(10)63365-2","article-title":"Heme oxygenase-1 modulates early inflammatory responses\u2013Evidence from the heme oxygenase-1-deficient mouse","volume":"165","author":"Kapturczak","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1042\/CS20100508","article-title":"Haem oxygenase-1 and cardiovascular disease: Mechanisms and therapeutic potential","volume":"120","author":"Chan","year":"2011","journal-title":"Clin. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.bcp.2018.01.017","article-title":"Regulation of vascular tone homeostasis by NO and H2S: Implications in hypertension","volume":"149","author":"Gheibi","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Munteanu, C., Turnea, M.A., and Rotariu, M. (2023). Hydrogen Sulfide: An Emerging Regulator of Oxidative Stress and Cellular Homeostasis\u2014A Comprehensive One-Year Review. Antioxidants, 12.","DOI":"10.3390\/antiox12091737"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.pharmthera.2012.09.007","article-title":"Carbon monoxide: Mechanisms of action and potential clinical implications","volume":"137","author":"Rochette","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/112_2017_7","article-title":"Gaseous Signaling Molecules in Cardiovascular Function: From Mechanisms to Clinical Translation","volume":"174","author":"Lee","year":"2018","journal-title":"Rev. Physiol. Biochem. Pharmacol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"da Silva, G.M., da Silva, M.C., Nascimento, D.V.G., Silva, E.M.L., Gouv\u00eaa, F.F.F., Lopes, L.G.D., Ara\u00fajo, A.V., Pereira, K.N.F., and de Queiroz, T.M. (2021). Nitric Oxide as a Central Molecule in Hypertension: Focus on the Vasorelaxant Activity of New Nitric Oxide Donors. Biology, 10.","DOI":"10.3390\/biology10101041"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1093\/eurheartj\/eht249","article-title":"More answers to the still unresolved question of nitrate tolerance","volume":"34","author":"Daiber","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.jhep.2023.06.017","article-title":"5-MTHF enhances the portal pressure reduction achieved with propranolol in patients with cirrhosis: A randomized placebo-controlled trial","volume":"79","author":"Vukotic","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"101590","DOI":"10.1016\/j.jacadv.2025.101590","article-title":"Nutritional L-Citrulline and Tetrahydrobiopterin in Peripheral Artery Disease A Phase II Randomized Trial (CIPER Study)","volume":"4","author":"Sedding","year":"2025","journal-title":"JACC Adv."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1161\/CIRCULATIONAHA.118.034757","article-title":"Cystathionine \u03b3 Lyase Sulfhydrates the RNA Binding Protein Human Antigen R to Preserve Endothelial Cell Function and Delay Atherogenesis","volume":"139","author":"Bibli","year":"2019","journal-title":"Circulation"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/1755-5922.12128","article-title":"A Novel Hydrogen Sulfide Prodrug, SG1002, Promotes Hydrogen Sulfide and Nitric Oxide Bioavailability in Heart Failure Patients","volume":"33","author":"Polhemus","year":"2015","journal-title":"Cardiovasc. Ther."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1111\/bph.12246","article-title":"The hydrogen sulfide donor, GYY4137, exhibits anti-atherosclerotic activity in high fat fed apolipoprotein E\u2212\/\u2212 mice","volume":"169","author":"Liu","year":"2013","journal-title":"Brit J. Pharmacol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.niox.2023.11.005","article-title":"Hydrogen sulfide attenuates atherosclerosis induced by low shear stress by sulfhydrylating endothelium NFIL3 to restrain MEST mediated endothelial mesenchymal transformation","volume":"142","author":"Zhou","year":"2024","journal-title":"Nitric Oxide-Biol. Chem."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1093\/biolre\/ioae103","article-title":"H2S donor GYY4137 mitigates sFlt-1-induced hypertension and vascular dysfunction in pregnant rats","volume":"111","author":"Yadav","year":"2024","journal-title":"Biol. Reprod."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2403284","DOI":"10.1002\/smll.202403284","article-title":"\u201cOne-Stone-Three-Birds\u201d H2S-Photothermal Therapy for Enhanced Thrombolysis and Vascular Healing","volume":"20","author":"Zheng","year":"2024","journal-title":"Small"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.1016\/j.transproceed.2007.08.063","article-title":"Carbon monoxide may reduce ischemia Reperfusion injury: A case report of complicated kidney transplantation from a carbon monoxide poisoned donor","volume":"39","author":"Bojakowski","year":"2007","journal-title":"Transplant. Proc."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1161\/ATVBAHA.120.315558","article-title":"Carbon Monoxide Suppresses Neointima Formation in Transplant Arteriosclerosis by Inhibiting Vascular Progenitor Cell Differentiation","volume":"41","author":"Sakihama","year":"2021","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"319","DOI":"10.4149\/BLL_2014_064","article-title":"The effect of induction of endogenous CO by heme-oxygenase inducer, hemin versus heme-oxygenase blocker, zinc mesoporphyrin on gastric secretion and ulceration under different conditions in adult male albino rats","volume":"115","author":"Ibrahim","year":"2014","journal-title":"Bratisl. Med. J."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"9612","DOI":"10.1039\/D4DT00087K","article-title":"Metal-based carbon monoxide releasing molecules with promising cytotoxic properties","volume":"53","author":"Mansour","year":"2024","journal-title":"Dalton Trans."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"109441","DOI":"10.1016\/j.intimp.2022.109441","article-title":"Carbon monoxide-releasing molecule 2 inhibits inflammation associated with intestinal ischemia-reperfusion injury in a rat model of hemorrhagic shock","volume":"113","author":"Niu","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1097\/TP.0000000000004007","article-title":"Luminal Administration of a Water-soluble Carbon Monoxide-releasing Molecule (CORM-3) Mitigates Ischemia\/Reperfusion Injury in Rats Following Intestinal Transplantation","volume":"106","author":"Obara","year":"2022","journal-title":"Transplantation"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/18\/9037\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:46:51Z","timestamp":1760035611000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/18\/9037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,17]]},"references-count":121,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26189037"],"URL":"https:\/\/doi.org\/10.3390\/ijms26189037","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,17]]}}}