{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T10:22:56Z","timestamp":1776421376232,"version":"3.51.2"},"reference-count":169,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,4,28]],"date-time":"2024-04-28T00:00:00Z","timestamp":1714262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Irisin is a myokine secreted under the influence of physical activity and exposure to low temperatures and through different exogenous stimuli by the cleavage of its precursor, fibronectin type III domain-containing protein 5 (FNDC5). It is mainly known for maintaining of metabolic homeostasis, promoting the browning of white adipose tissue, the thermogenesis process, and glucose homeostasis. Growing experimental evidence suggests the possible central role of irisin in the regulation of cardiometabolic pathophysiological processes. On the other side, hydrogen sulfide (H2S) is well recognized as a pleiotropic gasotransmitter that regulates several homeostatic balances and physiological functions and takes part in the pathogenesis of cardiometabolic diseases. Through the S-persulfidation of cysteine protein residues, H2S is capable of interacting with crucial signaling pathways, exerting beneficial effects in regulating glucose and lipid homeostasis as well. H2S and irisin seem to be intertwined; indeed, recently, H2S was found to regulate irisin secretion by activating the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1\u03b1)\/FNDC5\/irisin signaling pathway, and they share several mechanisms of action. Their involvement in metabolic diseases is confirmed by the detection of their lower circulating levels in obese and diabetic subjects. Along with the importance of metabolic disorders, these modulators exert favorable effects against cardiovascular diseases, preventing incidents of hypertension, atherosclerosis, heart failure, myocardial infarction, and ischemia\u2013reperfusion injury. This review, for the first time, aims to explore the role of H2S and irisin and their possible crosstalk in cardiovascular diseases, pointing out the main effects exerted through the common molecular pathways involved.<\/jats:p>","DOI":"10.3390\/antiox13050543","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T10:33:31Z","timestamp":1714559611000},"page":"543","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Hydrogen Sulfide and Irisin, Potential Allies in Ensuring Cardiovascular Health"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7899-0954","authenticated-orcid":false,"given":"Lorenzo","family":"Flori","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56120 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giada","family":"Benedetti","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56120 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Calderone","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56120 Pisa, Italy"},{"name":"Interdepartmental Research Center Nutrafood \u201cNutraceuticals and Food for Health\u201d, University of Pisa, 56120 Pisa, Italy"},{"name":"Interdepartmental Research Centre of Ageing Biology and Pathology, University of Pisa, 56120 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2431-6248","authenticated-orcid":false,"given":"Lara","family":"Testai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56120 Pisa, Italy"},{"name":"Interdepartmental Research Center Nutrafood \u201cNutraceuticals and Food for Health\u201d, University of Pisa, 56120 Pisa, Italy"},{"name":"Interdepartmental Research Centre of Ageing Biology and Pathology, University of Pisa, 56120 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/S0140-6736(11)60813-1","article-title":"The global obesity pandemic: Shaped by global drivers and local environments","volume":"378","author":"Swinburn","year":"2011","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105125","DOI":"10.1016\/j.phrs.2020.105125","article-title":"Role of hydrogen sulfide in cardiovascular ageing","volume":"160","author":"Testai","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jare.2020.05.015","article-title":"Role of hydrogen sulfide in endothelial dysfunction: Pathophysiology and therapeutic approaches","volume":"27","author":"Citi","year":"2021","journal-title":"J. Adv. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4380","DOI":"10.2174\/0929867325666180212120504","article-title":"The Role of Hydrogen Sulfide and H2S-donors in Myocardial Protection Against Ischemia\/Reperfusion Injury","volume":"25","author":"Citi","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"122491","DOI":"10.1016\/j.lfs.2024.122491","article-title":"Role of hydrogen sulfide in the regulation of lipid metabolism: Implications on cardiovascular health","volume":"341","author":"Flori","year":"2024","journal-title":"Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"118954","DOI":"10.1016\/j.lfs.2020.118954","article-title":"The \u201cirisin system\u201d: From biological roles to pharmacological and nutraceutical perspectives","volume":"267","author":"Flori","year":"2021","journal-title":"Life Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Grzeszczuk, M., Dzi\u0119giel, P., and Nowi\u0144ska, K. (2024). The Role of FNDC5\/Irisin in Cardiovascular Disease. Cells, 13.","DOI":"10.3390\/cells13030277"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Parsanathan, R., and Jain, S.K. (2022). Hydrogen Sulfide Regulates Irisin and Glucose Metabolism in Myotubes and Muscle of HFD-Fed Diabetic Mice. Antioxidants, 11.","DOI":"10.3390\/antiox11071369"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1002\/med.20234","article-title":"Hydrogen sulphide: Novel opportunity for drug discovery","volume":"32","author":"Martelli","year":"2012","journal-title":"Med. Res. Rev."},{"key":"ref_10","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_11","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.phrs.2012.12.005","article-title":"Vasorelaxation by hydrogen sulphide involves activation of Kv7 potassium channels","volume":"70","author":"Martelli","year":"2013","journal-title":"Pharmacol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6008","DOI":"10.1093\/emboj\/20.21.6008","article-title":"The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP) channel opener","volume":"20","author":"Zhao","year":"2001","journal-title":"EMBO J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3765","DOI":"10.1111\/bph.15516","article-title":"Involvement of 3\u2032,5\u2032-cyclic inosine monophosphate in cystathionine \u03b3-lyase-dependent regulation of the vascular tone","volume":"178","author":"Mitidieri","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.niox.2015.03.003","article-title":"Different patterns of H2S\/NO activity and cross-talk in the control of the coronary vascular bed under normotensive or hypertensive conditions","volume":"47","author":"Testai","year":"2015","journal-title":"Nitric Oxide"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Testai, L., Montanaro, R., Flori, L., Pagnotta, E., Vellecco, V., Gorica, E., Ugolini, L., Righetti, L., Brancaleone, V., and Bucci, M. (2023). Persulfidation of mitoKv7.4 channels contributes to the cardioprotective effects of the H(2)S-donor Erucin against ischemia\/reperfusion injury. Biochem. Pharmacol., 215.","DOI":"10.1016\/j.bcp.2023.115728"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Flori, L., Montanaro, R., Pagnotta, E., Ugolini, L., Righetti, L., Martelli, A., Di Cesare Mannelli, L., Ghelardini, C., Brancaleone, V., and Testai, L. (2023). Erucin Exerts Cardioprotective Effects on Ischemia\/Reperfusion Injury through the Modulation of mitoKATP Channels. Biomedicines, 11.","DOI":"10.3390\/biomedicines11123281"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/med.21332","article-title":"Mitochondrial potassium channels as pharmacological target for cardioprotective drugs","volume":"35","author":"Testai","year":"2015","journal-title":"Med. Res. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15","DOI":"10.33549\/physiolres.934928","article-title":"Hydrogen sulfide alleviates lipopolysaccharide-induced myocardial injury through TLR4-NLRP3 pathway","volume":"72","author":"Xia","year":"2023","journal-title":"Physiol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Donnarumma, E., Bhushan, S., Bradley, J.M., Otsuka, H., Donnelly, E.L., Lefer, D.J., and Islam, K.N. (2016). Nitrite Therapy Ameliorates Myocardial Dysfunction via H2S and Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2)-Dependent Signaling in Chronic Heart Failure. J. Am. Hear. Assoc., 5.","DOI":"10.1161\/JAHA.116.003551"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1006\/bbrc.1997.6878","article-title":"The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide","volume":"237","author":"Hosoki","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"H2316","DOI":"10.1152\/ajpheart.00331.2004","article-title":"Hydrogen sulfide-induced relaxation of resistance mesenteric artery beds of rats","volume":"287","author":"Cheng","year":"2004","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1124\/mol.105.017467","article-title":"Direct stimulation of K(ATP) channels by exogenous and endogenous hydrogen sulfide in vascular smooth muscle cells","volume":"68","author":"Tang","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.bbrc.2006.02.154","article-title":"Evidence for the formation of a novel nitrosothiol from the gaseous mediators nitric oxide and hydrogen sulphide","volume":"343","author":"Whiteman","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/sj.bjp.0706906","article-title":"Regulation of vascular nitric oxide in vitro and in vivo; a new role for endogenous hydrogen sulphide?","volume":"149","author":"Ali","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1161\/CIRCULATIONAHA.113.002208","article-title":"Decreased endogenous production of hydrogen sulfide accelerates atherosclerosis","volume":"127","author":"Mani","year":"2013","journal-title":"Circulation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1126\/science.1162667","article-title":"H2S as a physiologic vasorelaxant: Hypertension in mice with deletion of cystathionine gamma-lyase","volume":"322","author":"Yang","year":"2008","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1139\/y03-077","article-title":"Modulation of endogenous production of H2S in rat tissues","volume":"81","author":"Zhao","year":"2003","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1161\/CIRCULATIONAHA.112.000855","article-title":"H\u2082S 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_29","doi-asserted-by":"crossref","first-page":"21972","DOI":"10.1073\/pnas.0908047106","article-title":"Hydrogen sulfide is an endogenous stimulator of angiogenesis","volume":"106","author":"Papapetropoulos","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1007\/s00210-016-1244-4","article-title":"Decreased vascular H2S production is associated with vascular oxidative stress in rats fed a high-fat western diet","volume":"389","author":"Jenkins","year":"2016","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/bjp.2008.296","article-title":"Biosynthesis of H2S is impaired in non-obese diabetic (NOD) mice","volume":"155","author":"Brancaleone","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1089\/ars.2009.2956","article-title":"Low levels of hydrogen sulfide in the blood of diabetes patients and streptozotocin-treated rats causes vascular inflammation?","volume":"12","author":"Jain","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13829","DOI":"10.1073\/pnas.1105121108","article-title":"Hydrogen sulfide replacement therapy protects the vascular endothelium in hyperglycemia by preserving mitochondrial function","volume":"108","author":"Suzuki","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1089\/ars.2009.2899","article-title":"The effect of hydrogen sulfide donors on lipopolysaccharide-induced formation of inflammatory mediators in macrophages","volume":"12","author":"Whiteman","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2119\/molmed.2015.00035","article-title":"Regulation of Vascular Tone, Angiogenesis and Cellular Bioenergetics by the 3-Mercaptopyruvate Sulfurtransferase\/H2S Pathway: Functional Impairment by Hyperglycemia and Restoration by DL-\u03b1-Lipoic Acid","volume":"21","author":"Coletta","year":"2015","journal-title":"Mol. Med."},{"key":"ref_36","first-page":"951","article-title":"Changes of the new gaseous transmitter H2S in patients with coronary heart disease","volume":"25","author":"Jiang","year":"2005","journal-title":"Di Yi Jun Yi Da Xue Xue Bao"},{"key":"ref_37","first-page":"768607","article-title":"The cardioprotective actions of hydrogen sulfide in acute myocardial infarction and heart failure","volume":"2014","author":"Polhemus","year":"2014","journal-title":"Scientifica (Cairo)"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Piragine, E., Malanima, M.A., Lucenteforte, E., Martelli, A., and Calderone, V. (2023). Circulating Levels of Hydrogen Sulfide (H(2)S) in Patients with Age-Related Diseases: A Systematic Review and Meta-Analysis. Biomolecules, 13.","DOI":"10.3390\/biom13071023"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.bbalip.2017.11.008","article-title":"Cystathionine gamma-lyase\/hydrogen sulfide system is essential for adipogenesis and fat mass accumulation in mice","volume":"1863","author":"Yang","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.bbrc.2019.10.192","article-title":"Sulfhydration of perilipin 1 is involved in the inhibitory effects of cystathionine gamma lyase\/hydrogen sulfide on adipocyte lipolysis","volume":"521","author":"Ding","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"36359","DOI":"10.1038\/srep36359","article-title":"A Comparative Metabolomics Approach Reveals Early Biomarkers for Metabolic Response to Acute Myocardial Infarction","volume":"6","author":"Ali","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1161\/ATVBAHA.108.179333","article-title":"Role of hydrogen sulfide in the development of atherosclerotic lesions in apolipoprotein E knockout mice","volume":"29","author":"Wang","year":"2009","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jare.2019.11.010","article-title":"Point-of-care testing and optimization of sample treatment for fluorometric determination of hydrogen sulphide in plasma of cardiovascular patients","volume":"27","author":"Alyan","year":"2021","journal-title":"J. Adv. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.bbagen.2013.05.037","article-title":"Chemical aspects of hydrogen sulfide measurements in physiological samples","volume":"1840","author":"Nagy","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nature10777","article-title":"A PGC1-\u03b1-dependent myokine that drives brown-fat-like development of white fat and thermogenesis","volume":"481","author":"Wu","year":"2012","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Mancinelli, R., Checcaglini, F., Coscia, F., Gigliotti, P., Fulle, S., and Fan\u00f2-Illic, G. (2021). Biological Aspects of Selected Myokines in Skeletal Muscle: Focus on Aging. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168520"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1016\/j.cell.2018.10.025","article-title":"Irisin Mediates Effects on Bone and Fat via \u03b1V Integrin Receptors","volume":"175","author":"Kim","year":"2018","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1159\/000494655","article-title":"Interaction of CREB and PGC-1\u03b1 Induces Fibronectin Type III Domain-Containing Protein 5 Expression in C2C12 Myotubes","volume":"50","author":"Yang","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Chen, S.Q., Ding, L.N., Zeng, N.X., Liu, H.M., Zheng, S.H., Xu, J.W., and Li, R.M. (2019). Icariin induces irisin\/FNDC5 expression in C2C12 cells via the AMPK pathway. Biomed. Pharmacother., 115.","DOI":"10.1016\/j.biopha.2019.108930"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/sms.12904","article-title":"Effect of an acute exercise bout on immediate post-exercise irisin concentration in adults: A meta-analysis","volume":"28","author":"Fox","year":"2018","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"923","DOI":"10.5603\/FM.a2021.0107","article-title":"The effects of irisin on the rat thoracic aorta: A histological study","volume":"81","author":"Altaweel","year":"2022","journal-title":"Folia Morphol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Song, H., Zhang, Y., Wu, F., Mu, Q., Jiang, M., Wang, F., Zhang, W., Li, L., and Shao, L. (2016). Irisin Inhibits Atherosclerosis by Promoting Endothelial Proliferation Through microRNA126-5p. J. Am. Hear. Assoc., 5.","DOI":"10.1161\/JAHA.116.004031"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Wu, F., Song, H., Zhang, Y., Zhang, Y., Mu, Q., Jiang, M., Wang, F., Zhang, W., Li, L., and Li, H. (2015). Irisin Induces Angiogenesis in Human Umbilical Vein Endothelial Cells In Vitro and in Zebrafish Embryos In Vivo via Activation of the ERK Signaling Pathway. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134662"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"170685","DOI":"10.1016\/j.peptides.2021.170685","article-title":"Physiological role of K(+) channels in irisin-induced vasodilation in rat thoracic aorta","volume":"147","author":"Demirel","year":"2022","journal-title":"Peptides"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1016\/j.bbrc.2018.07.005","article-title":"Excessive irisin increases oxidative stress and apoptosis in murine heart","volume":"503","author":"Ho","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1530\/JME-19-0123","article-title":"FNDC5\/Irisin counteracts lipotoxic-induced apoptosis in hypoxic H9c2 cells","volume":"63","author":"Moscoso","year":"2019","journal-title":"J. Mol. Endocrinol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3775","DOI":"10.1002\/jcp.25857","article-title":"Irisin plays a pivotal role to protect the heart against ischemia and reperfusion injury","volume":"232","author":"Wang","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e166","DOI":"10.1002\/ctm2.166","article-title":"Irisin attenuates myocardial ischemia\/reperfusion-induced cardiac dysfunction by regulating ER-mitochondria interaction through a mitochondrial ubiquitin ligase-dependent mechanism","volume":"10","author":"Lu","year":"2020","journal-title":"Clin. Transl. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"620608","DOI":"10.3389\/fphys.2021.620608","article-title":"Irisin: A New Code Uncover the Relationship of Skeletal Muscle and Cardiovascular Health During Exercise","volume":"12","author":"Ma","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1002\/cbin.11763","article-title":"FNDC5\/irisin reduces ferroptosis and improves mitochondrial dysfunction in hypoxic cardiomyocytes by Nrf2\/HO-1 axis","volume":"46","author":"Cao","year":"2022","journal-title":"Cell Biol. Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/s41467-017-02795-4","article-title":"AMPK activation counteracts cardiac hypertrophy by reducing O-GlcNAcylation","volume":"9","author":"Mailleux","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1042\/CS20190016","article-title":"FNDC5\/Irisin inhibits pathological cardiac hypertrophy","volume":"133","author":"Yu","year":"2019","journal-title":"Clin. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.metabol.2017.05.002","article-title":"Circulating irisin levels are lower in patients with either stable coronary artery disease (CAD) or myocardial infarction (MI) versus healthy controls, whereas follistatin and activin A levels are higher and can discriminate MI from CAD with similar to CK-MB accuracy","volume":"73","author":"Anastasilakis","year":"2017","journal-title":"Metabolism"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4193","DOI":"10.12659\/MSM.897376","article-title":"Association of Serum Irisin Concentrations with Presence and Severity of Coronary Artery Disease","volume":"22","author":"Deng","year":"2016","journal-title":"Med. Sci. Monit."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"61","DOI":"10.23736\/S0391-1977.17.02663-3","article-title":"Lower irisin levels in coronary artery disease: A meta-analysis","volume":"45","author":"Guo","year":"2020","journal-title":"Minerva Endocrinol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.amjms.2021.02.020","article-title":"Association of Circulating Irisin Levels and the Characteristics and Prognosis of Coronary Artery Disease","volume":"362","author":"Pan","year":"2021","journal-title":"Am. J. Med Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.peptides.2014.04.002","article-title":"Decreased saliva\/serum irisin concentrations in the acute myocardial infarction promising for being a new candidate biomarker for diagnosis of this pathology","volume":"56","author":"Aydin","year":"2014","journal-title":"Peptides"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1139\/cjpp-2018-0736","article-title":"Serum irisin level in myocardial infarction patients with or without heart failure","volume":"97","author":"Galal","year":"2019","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ijcard.2017.11.072","article-title":"Serum irisin levels are associated with adverse cardiovascular outcomes in patients with acute myocardial infarction","volume":"261","author":"Hsieh","year":"2018","journal-title":"Int. J. Cardiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"894171","DOI":"10.3389\/fimmu.2022.894171","article-title":"Irisin as a Novel Biomarker of Subclinical Atherosclerosis, Cardiovascular Risk and Severe Disease in Axial Spondyloarthritis","volume":"13","author":"Corrales","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Saadeldin, M.K., Elshaer, S.S., Emara, I.A., Maged, M., and Abdel-Aziz, A.K. (2018). Serum sclerostin and irisin as predictive markers for atherosclerosis in Egyptian type II diabetic female patients: A case control study. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0206761"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.dsx.2018.11.050","article-title":"The association between serum irisin levels and cardiovascular disease in diabetic patients","volume":"13","author":"Khorasani","year":"2019","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_73","unstructured":"Fu, S., and Xing, G. (Altern. Ther. Health Med., 2024). Changes in Serum Irisin Levels and Their Significance in Carotid Atherosclerosis Associated with Obesity, Altern. Ther. Health Med., online ahead of print."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e403","DOI":"10.1002\/edm2.403","article-title":"Evaluation of serum levels of Irisin as a marker of endothelial dysfunction in patients with type 2 diabetes mellitus","volume":"6","author":"Ahmed","year":"2023","journal-title":"Endocrinol. Diabetes Metab."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"6052","DOI":"10.21037\/apm-21-406","article-title":"Lower serum irisin levels are associated with the increasing mortality of cardiovascular and cerebrovascular diseases in hemodialysis patients","volume":"10","author":"Dong","year":"2021","journal-title":"Ann. Palliat. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"154303","DOI":"10.1016\/j.cyto.2018.02.017","article-title":"Serum levels of irisin predict short-term outcomes in ischemic stroke","volume":"122","author":"Wu","year":"2019","journal-title":"Cytokine"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1038\/s41440-019-0266-y","article-title":"The Role of Myokines and Adipokines in Hypertension and Hypertension-related Complications","volume":"42","author":"Chen","year":"2019","journal-title":"Hypertens. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.numecd.2018.04.009","article-title":"High irisin levels in overweight\/obese children and its positive correlation with metabolic profile, blood pressure, and endothelial progenitor cells","volume":"28","author":"Oliveira","year":"2018","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1530\/EJE-13-1053","article-title":"Serum levels of the myokine irisin in relation to metabolic and renal function","volume":"170","author":"Ebert","year":"2014","journal-title":"Eur. J. Endocrinol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1080\/10641963.2016.1273945","article-title":"Expressions of irisin and urotensin II and their relationships with blood pressure in patients with preeclampsia","volume":"39","author":"Zhang","year":"2017","journal-title":"Clin. Exp. Hypertens."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.niox.2014.11.006","article-title":"Hydrogen sulfide protects against apoptosis under oxidative stress through SIRT1 pathway in H9c2 cardiomyocytes","volume":"46","author":"Wu","year":"2015","journal-title":"Nitric Oxide"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1536\/ihj.15-506","article-title":"Exogenous Hydrogen Sulfide Postconditioning Protects Isolated Rat Hearts From Ischemia\/Reperfusion Injury Through Sirt1\/PGC-1\u03b1 Signaling Pathway","volume":"57","author":"Hu","year":"2016","journal-title":"Int. Hear. J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2174649","DOI":"10.1080\/13510002.2023.2174649","article-title":"Cystathionine \u03b3-lyase S-sulfhydrates SIRT1 to attenuate myocardial death in isoprenaline-induced heart failure","volume":"28","author":"Wu","year":"2023","journal-title":"Redox Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.yjmcc.2018.01.011","article-title":"Hydrogen sulfide regulates cardiac mitochondrial biogenesis via the activation of AMPK","volume":"116","author":"Shimizu","year":"2018","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"621","DOI":"10.2147\/DDDT.S242521","article-title":"Hydrogen Sulfide Protects Against High Glucose-Induced Human Umbilical Vein Endothelial Cell Injury Through Activating PI3K\/Akt\/eNOS Pathway","volume":"14","author":"Lin","year":"2020","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"R443","DOI":"10.1152\/ajpregu.00088.2013","article-title":"Akt\/eNOS signaling and PLN S-sulfhydration are involved in H\u2082S-dependent cardiac effects in frog and rat","volume":"305","author":"Mazza","year":"2013","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3751","DOI":"10.3760\/cma.j.issn.0366-6999.20141573","article-title":"Hydrogen sulfide defends against the cardiovascular risk of Nw-nitro-L-argininemethyl ester-induced hypertension in rats via the nitric oxide\/endothelial nitric oxide synthase pathway","volume":"127","author":"Ji","year":"2014","journal-title":"Chin. Med. J."},{"key":"ref_88","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_89","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1177\/1535370217732325","article-title":"Hydrogen sulfide ameliorated L-NAME-induced hypertensive heart disease by the Akt\/eNOS\/NO pathway","volume":"242","author":"Jin","year":"2017","journal-title":"Exp. Biol. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3182","DOI":"10.1073\/pnas.1321871111","article-title":"Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent","volume":"111","author":"King","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"H1501","DOI":"10.1152\/ajpheart.00443.2015","article-title":"Irisin improves endothelial function in obese mice through the AMPK-eNOS pathway","volume":"309","author":"Han","year":"2015","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Fu, J., Han, Y., Wang, J., Liu, Y., Zheng, S., Zhou, L., Jose, P.A., and Zeng, C. (2016). Irisin Lowers Blood Pressure by Improvement of Endothelial Dysfunction via AMPK-Akt-eNOS-NO Pathway in the Spontaneously Hypertensive Rat. J. Am. Hear. Assoc., 5.","DOI":"10.1161\/JAHA.116.003433"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.atherosclerosis.2015.10.020","article-title":"Irisin protects against endothelial injury and ameliorates atherosclerosis in apolipoprotein E-Null diabetic mice","volume":"243","author":"Lu","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s00109-014-1227-1","article-title":"Hydrogen sulfide upregulates KATP channel expression in vascular smooth muscle cells of spontaneously hypertensive rats","volume":"93","author":"Sun","year":"2015","journal-title":"J. Mol. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1161\/CIRCRESAHA.111.240242","article-title":"Hydrogen sulfide as endothelium-derived hyperpolarizing factor sulfhydrates potassium channels","volume":"109","author":"Mustafa","year":"2011","journal-title":"Circ. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1097\/01.shk.0000225722.56681.64","article-title":"The production of hydrogen sulfide limits myocardial ischemia and reperfusion injury and contributes to the cardioprotective effects of preconditioning with endotoxin, but not ischemia in the rat","volume":"26","author":"Sivarajah","year":"2006","journal-title":"Shock"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.phrs.2016.09.006","article-title":"The novel H(2)S-donor 4-carboxyphenyl isothiocyanate promotes cardioprotective effects against ischemia\/reperfusion injury through activation of mitoK(ATP) channels and reduction of oxidative stress","volume":"113","author":"Testai","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_98","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_99","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1124\/jpet.121.001017","article-title":"Targeting Mitochondrial Large-Conductance Calcium-Activated Potassium Channel by Hydrogen Sulfide via Heme-Binding Site","volume":"381","author":"Walewska","year":"2022","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s10557-015-6580-y","article-title":"Central and peripheral irisin differentially regulate blood pressure","volume":"29","author":"Zhang","year":"2015","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.bbrc.2017.10.160","article-title":"TRPV4 is involved in irisin-induced endothelium-dependent vasodilation","volume":"495","author":"Ye","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"H1215","DOI":"10.1152\/ajpheart.00796.2012","article-title":"Hydrogen sulfide preconditions the db\/db diabetic mouse heart against ischemia-reperfusion injury by activating Nrf2 signaling in an Erk-dependent manner","volume":"304","author":"Peake","year":"2013","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1161\/CIRCRESAHA.109.199919","article-title":"Hydrogen sulfide mediates cardioprotection through Nrf2 signaling","volume":"105","author":"Calvert","year":"2009","journal-title":"Circ. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e002368","DOI":"10.1161\/CIRCHEARTFAILURE.115.002368","article-title":"Sodium Sulfide Attenuates Ischemic-Induced Heart Failure by Enhancing Proteasomal Function in an Nrf2-Dependent Manner","volume":"9","author":"Shimizu","year":"2016","journal-title":"Circ. Hear. Fail."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"18951","DOI":"10.1002\/jcp.28535","article-title":"Irisin attenuates oxidized low-density lipoprotein impaired angiogenesis through AKT\/mTOR\/S6K1\/Nrf2 pathway","volume":"234","author":"Zhang","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"109170","DOI":"10.1016\/j.diabres.2021.109170","article-title":"Irisin rescues diabetic cardiac microvascular injury via ERK1\/2\/Nrf2\/HO-1 mediated inhibition of oxidative stress","volume":"183","author":"Zhu","year":"2022","journal-title":"Diabetes Res. Clin. Pr."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Mazur-Bialy, A.I., and Poche\u0107, E. (2021). The Time-Course of Antioxidant Irisin Activity: Role of the Nrf2\/HO-1\/HMGB1 Axis. Antioxidants, 10.","DOI":"10.3390\/antiox10010088"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"94","DOI":"10.7555\/JBR.33.20190071","article-title":"H (2)S protects against diabetes-accelerated atherosclerosis by preventing the activation of NLRP3 inflammasome","volume":"34","author":"Zheng","year":"2019","journal-title":"J. Biomed. Res."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Zhou, T., Qian, H., Zheng, N., Lu, Q., and Han, Y. (2022). GYY4137 ameliorates sepsis-induced cardiomyopathy via NLRP3 pathway. Biochim. Biophys. Acta Mol. Basis Dis., 1868.","DOI":"10.1016\/j.bbadis.2022.166497"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"119466","DOI":"10.1016\/j.lfs.2021.119466","article-title":"Hydrogen sulfide reduces pyroptosis and alleviates ischemia-reperfusion-induced acute kidney injury by inhibiting NLRP3 inflammasome","volume":"284","author":"Ni","year":"2021","journal-title":"Life Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41420-021-00434-y","article-title":"NLRP3-mediated pyroptosis aggravates pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction in mice: Cardioprotective role of irisin","volume":"7","author":"Yue","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1159\/000481758","article-title":"Exogenous H2S Protects Against Diabetic Cardiomyopathy by Activating Autophagy via the AMPK\/mTOR Pathway","volume":"43","author":"Yang","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_113","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":"2015","journal-title":"Mol. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1002\/cbin.11441","article-title":"Irisin ameliorates high glucose-induced cardiomyocytes injury via AMPK\/mTOR signal pathway","volume":"44","author":"Deng","year":"2020","journal-title":"Cell Biol. Int."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"691070","DOI":"10.1155\/2015\/691070","article-title":"Hydrogen Sulfide Donor GYY4137 Protects against Myocardial Fibrosis","volume":"2015","author":"Meng","year":"2015","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_116","first-page":"549","article-title":"Exogenous H2S mitigates myocardial fibrosis in diabetic rats through suppression of the canonical Wnt pathway","volume":"44","author":"Yang","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Wang, F.Z., Zhou, H., Wang, H.Y., Dai, H.B., Gao, Q., Qian, P., and Zhou, Y.B. (2021). Hydrogen sulfide prevents arterial medial calcification in rats with diabetic nephropathy. BMC Cardiovasc. Disord., 21.","DOI":"10.1186\/s12872-021-02307-9"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4196\/kjpp.2023.27.1.1","article-title":"Hydrogen sulfide alleviates hypothyroidism-induced myocardial fibrosis in rats through stimulating autophagy and inhibiting TGF-\u03b21\/Smad2 pathway","volume":"27","author":"Song","year":"2023","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_119","first-page":"717","article-title":"Irisin attenuates angiotensin II-induced atrial fibrillation and atrial fibrosis via LOXL2 and TGF\u03b21\/Smad2\/3 signaling pathways","volume":"26","author":"Wu","year":"2023","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1016\/j.tjnut.2023.08.024","article-title":"Hydrogen Sulfide Regulates Glucose Uptake in Skeletal Muscles via S-Sulfhydration of AMPK in Muscle Fiber Type-Dependent Way","volume":"153","author":"Li","year":"2023","journal-title":"J. Nutr."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"3416","DOI":"10.1210\/en.2017-00391","article-title":"Hydrogen Sulfide and Sulfate Prebiotic Stimulates the Secretion of GLP-1 and Improves Glycemia in Male Mice","volume":"158","author":"Pichette","year":"2017","journal-title":"Endocrinology"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"917","DOI":"10.3892\/ijmm.2013.1462","article-title":"Exogenous hydrogen sulfide protects H9c2 cardiac cells against high glucose-induced injury by inhibiting the activities of the p38 MAPK and ERK1\/2 pathways","volume":"32","author":"Xu","year":"2013","journal-title":"Int. J. Mol. Med."},{"key":"ref_123","first-page":"E791","article-title":"Irisin counteracts high glucose and fatty acid-induced cytotoxicity by preserving the AMPK-insulin receptor signaling axis in C2C12 myoblasts","volume":"318","author":"Yano","year":"2020","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1042\/CS20150009","article-title":"Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the PI3K\/Akt pathway in type 2 diabetic mice and hepatocytes","volume":"129","author":"Liu","year":"2015","journal-title":"Clin. Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.yexcr.2017.09.006","article-title":"\u03b2-arrestin-2 is involved in irisin induced glucose metabolism in type 2 diabetes via p38 MAPK signaling","volume":"360","author":"Pang","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1210\/me.2014-1353","article-title":"Irisin, a Novel Myokine, Regulates Glucose Uptake in Skeletal Muscle Cells via AMPK","volume":"29","author":"Lee","year":"2015","journal-title":"Mol. Endocrinol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1089\/ars.2017.7195","article-title":"Sulfhydrated Sirtuin-1 Increasing Its Deacetylation Activity Is an Essential Epigenetics Mechanism of Anti-Atherogenesis by Hydrogen Sulfide","volume":"30","author":"Du","year":"2019","journal-title":"Antioxid. Redox Signal."},{"key":"ref_128","first-page":"1850","article-title":"PGC-1 mediates the regulation of metformin in muscle irisin expression and function","volume":"7","author":"Yang","year":"2015","journal-title":"Am. J. Transl. Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jnutbio.2019.03.012","article-title":"Genistein increases the thermogenic program of subcutaneous WAT and increases energy expenditure in mice","volume":"68","author":"Noriega","year":"2019","journal-title":"J. Nutr. Biochem."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Andrade, J.M.O., Barcala-Jorge, A.S., Batista-Jorge, G.C., Para\u00edso, A.F., Freitas, K.M., Lelis, D.F., Guimar\u00e3es, A.L.S., de Paula, A.M.B., and Santos, S.H.S. (2019). Effect of resveratrol on expression of genes involved thermogenesis in mice and humans. Biomed. Pharmacother., 112.","DOI":"10.1016\/j.biopha.2019.108634"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1161\/01.ATV.0000051384.43104.FC","article-title":"Endothelial dysfunction: A marker of atherosclerotic risk","volume":"23","author":"Bonetti","year":"2003","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1007\/s11255-013-0428-9","article-title":"High FFA levels related to microalbuminuria and uncoupling of VEGF-NO axis in obese rats","volume":"45","author":"Sun","year":"2013","journal-title":"Int. Urol. Nephrol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"C3","DOI":"10.1152\/ajpcell.00282.2016","article-title":"Hydrogen sulfide, an enhancer of vascular nitric oxide signaling: Mechanisms and implications","volume":"312","author":"Szabo","year":"2017","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_134","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_135","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1097\/FJC.0000000000000386","article-title":"Irisin Increased the Number and Improved the Function of Endothelial Progenitor Cells in Diabetes Mellitus Mice","volume":"68","author":"Zhu","year":"2016","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_136","first-page":"G1266","article-title":"H2S contributes to the hepatic arterial buffer response and mediates vasorelaxation of the hepatic artery via activation of K(ATP) channels","volume":"295","author":"Siebert","year":"2008","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/med.10060","article-title":"KATP channel openers: Structure-activity relationships and therapeutic potential","volume":"24","author":"Mannhold","year":"2004","journal-title":"Med. Res. Rev."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1152\/physrev.1997.77.4.1165","article-title":"ATP-sensitive and inwardly rectifying potassium channels in smooth muscle","volume":"77","author":"Quayle","year":"1997","journal-title":"Physiol. Rev."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1152\/physrev.00003.2015","article-title":"KATP Channels in the Cardiovascular System","volume":"96","author":"Foster","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1139\/Y07-120","article-title":"Hydrogen sulfide contributes to cardioprotection during ischemia-reperfusion injury by opening K ATP channels","volume":"85","author":"Zhang","year":"2007","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1097\/FJC.0b013e318279ba42","article-title":"TRPV4 and the regulation of vascular tone","volume":"61","author":"Filosa","year":"2013","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"e00199","DOI":"10.1002\/phy2.199","article-title":"Characterization of blood pressure and endothelial function in TRPV4-deficient mice with l-NAME- and angiotensin II-induced hypertension","volume":"2","author":"Nishijima","year":"2014","journal-title":"Physiol. Rep."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"H466","DOI":"10.1152\/ajpheart.00854.2009","article-title":"TRPV4-mediated endothelial Ca2+ influx and vasodilation in response to shear stress","volume":"298","author":"Mendoza","year":"2010","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Loh, Y.C., Tan, C.S., Ch\u2019ng, Y.S., Yeap, Z.Q., Ng, C.H., and Yam, M.F. (2018). Overview of the Microenvironment of Vasculature in Vascular Tone Regulation. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010120"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"219","DOI":"10.33549\/physiolres.933952","article-title":"Downregulation of endothelial transient receptor potential vanilloid type 4 channel underlines impaired endothelial nitric oxide-mediated relaxation in the mesenteric arteries of hypertensive rats","volume":"68","author":"Boudaka","year":"2019","journal-title":"Physiol. Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1002\/mc.20465","article-title":"Molecular mechanisms of Nrf2-mediated antioxidant response","volume":"48","author":"Li","year":"2009","journal-title":"Mol. Carcinog."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.bbadis.2016.11.005","article-title":"Nrf2 signaling pathway: Pivotal roles in inflammation","volume":"1863","author":"Ahmed","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1089\/ars.2012.4645","article-title":"Hydrogen sulfide protects against cellular senescence via S-sulfhydration of Keap1 and activation of Nrf2","volume":"18","author":"Yang","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1089\/ars.2012.4944","article-title":"The gasotransmitter hydrogen sulfide induces nrf2-target genes by inactivating the keap1 ubiquitin ligase substrate adaptor through formation of a disulfide bond between cys-226 and cys-613","volume":"19","author":"Hourihan","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"205","DOI":"10.2174\/1570161120666220510120220","article-title":"Current Insights on the Role of Irisin in Endothelial Dysfunction","volume":"20","year":"2022","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"108053","DOI":"10.1016\/j.pharmthera.2021.108053","article-title":"Targeting the NLRP3 inflammasome in cardiovascular diseases","volume":"236","author":"Toldo","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.7150\/ijbs.47595","article-title":"Hydrogen Sulfide Plays an Important Role by Influencing NLRP3 inflammasome","volume":"16","author":"Wang","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.molcel.2010.09.023","article-title":"Autophagy and the integrated stress response","volume":"40","author":"Kroemer","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_154","first-page":"E925","article-title":"Hydrogen sulfide reduces serum triglyceride by activating liver autophagy via the AMPK-mTOR pathway","volume":"309","author":"Sun","year":"2015","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0092-8674(03)00432-X","article-title":"Mechanisms of TGF-beta signaling from cell membrane to the nucleus","volume":"113","author":"Shi","year":"2003","journal-title":"Cell"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1254\/jphs.11065FP","article-title":"Effect of efonidipine on TGF-\u03b21-induced cardiac fibrosis through Smad2-dependent pathway in rat cardiac fibroblasts","volume":"117","author":"Lei","year":"2011","journal-title":"J. Pharmacol. Sci."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Hata, A., and Chen, Y.G. (2016). TGF-\u03b2 Signaling from Receptors to Smads. Cold Spring Harb. Perspect. Biol., 8.","DOI":"10.1101\/cshperspect.a022061"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Testai, L., Brancaleone, V., Flori, L., Montanaro, R., and Calderone, V. (2021). Modulation of EndMT by Hydrogen Sulfide in the Prevention of Cardiovascular Fibrosis. Antioxidants, 10.","DOI":"10.3390\/antiox10060910"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1056\/NEJMoa021778","article-title":"Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes","volume":"348","author":"Gaede","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Horita, S., Nakamura, M., Suzuki, M., Satoh, N., Suzuki, A., and Seki, G. (2016). Selective Insulin Resistance in the Kidney. Biomed. Res. Int., 2016.","DOI":"10.1155\/2016\/5825170"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/embor.2010.160","article-title":"MAPK signalling in cellular metabolism: Stress or wellness?","volume":"11","author":"Gehart","year":"2010","journal-title":"EMBO Rep."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jare.2020.02.013","article-title":"Hydrogen sulfide regulates insulin secretion and insulin resistance in diabetes mellitus, a new promising target for diabetes mellitus treatment? A review","volume":"27","author":"Zhang","year":"2021","journal-title":"J. Adv. Res."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Xu, M., Liu, X., Bao, P., Wang, Y., Zhu, X., Liu, Y., Ni, X., and Lu, J. (2022). Skeletal Muscle CSE Deficiency Leads to Insulin Resistance in Mice. Antioxidants, 11.","DOI":"10.3390\/antiox11112216"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Marrano, N., Biondi, G., Borrelli, A., Cignarelli, A., Perrini, S., Laviola, L., Giorgino, F., and Natalicchio, A. (2021). Irisin and Incretin Hormones: Similarities, Differences, and Implications in Type 2 Diabetes and Obesity. Biomolecules, 11.","DOI":"10.3390\/biom11020286"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1002\/med.21913","article-title":"Progress and perspective on hydrogen sulfide donors and their biomedical applications","volume":"42","author":"Song","year":"2022","journal-title":"Med. Res. Rev."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1055\/s-0034-1368591","article-title":"Hydrogen sulfide releasing capacity of natural isothiocyanates: Is it a reliable explanation for the multiple biological effects of Brassicaceae?","volume":"80","author":"Citi","year":"2014","journal-title":"Planta Med."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"17977","DOI":"10.1073\/pnas.0705710104","article-title":"Hydrogen sulfide mediates the vasoactivity of garlic","volume":"104","author":"Benavides","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Citi, V., Passerini, M., Calderone, V., and Testai, L. (2023). Plants and Mushrooms as Possible New Sources of H(2)S Releasing Sulfur Compounds. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241511886"},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Casertano, M., Esposito, E., Bello, I., Indolfi, C., Putra, M.Y., Di Cesare Mannelli, L., Ghelardini, C., Menna, M., Sorrentino, R., and Cirino, G. (2023). Searching for Novel Sources of Hydrogen Sulfide Donors: Chemical Profiling of Polycarpa aurata Extract and Evaluation of the Anti-Inflammatory Effects. Mar. Drugs, 21.","DOI":"10.3390\/md21120641"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/5\/543\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:35:35Z","timestamp":1760106935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/5\/543"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,28]]},"references-count":169,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["antiox13050543"],"URL":"https:\/\/doi.org\/10.3390\/antiox13050543","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,28]]}}}