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Melatonin, an endogenously produced molecule, experimentally reduces the initiation and progression of atherosclerotic lesions, which are often the basis of coronary artery disease. The current review critically analyzes published data related to the experimental use of melatonin to forestall coronary artery pathologies. Collectively, these studies document melatonin\u2019s anti-atherosclerotic actions in reducing LDL oxidation and triglyceride levels, lowering endothelial malfunction, limiting adhesion molecule formation, preventing macrophage polarization to the M1 pro-inflammatory phenotype, changing cellular metabolism, scavenging destructive reactive oxygen species, preventing the proliferation and invasion of arterial smooth muscle cells into the lesioned area, restricting the ingrowth of blood vessels from the vasa vasorum, and solidifying the plaque cap to reduce the chance of its rupture. Diabetic hyperglycemia, which aggravates atherosclerotic plaque formation, is also inhibited by melatonin supplementation in experimental animals. The potential value of non-toxic melatonin as a possible inhibitor of cardiac pathology in humans should be seriously considered by performing clinical trials using this multifunctional molecule.<\/jats:p>","DOI":"10.3390\/life14010088","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T05:12:17Z","timestamp":1704431537000},"page":"88","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Mitochondrial Melatonin: Beneficial Effects in Protecting against Heart Failure"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6763-4225","authenticated-orcid":false,"given":"Russel J.","family":"Reiter","sequence":"first","affiliation":[{"name":"Department of Cell Systems and Anatomy, Long School of Medicine, UT Health San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2346-5305","authenticated-orcid":false,"given":"Ramaswamy","family":"Sharma","sequence":"additional","affiliation":[{"name":"Applied Biomedical Sciences, School of Osteopathic Medicine, University of the Incarnate Word, San Antonio, TX 78235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Gustavo de Almeida","family":"Chuffa","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology-IBB\/UNESP, Institute of Biosciences of Botucatu, Universidade Estadual Paulista, Botucatu 18618-689, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9922-4885","authenticated-orcid":false,"given":"Fedor","family":"Simko","sequence":"additional","affiliation":[{"name":"Institute of Pathophysiology, Faculty of Medicine, Comenius University, 81108 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6384-6893","authenticated-orcid":false,"given":"Alberto","family":"Dominguez-Rodriguez","sequence":"additional","affiliation":[{"name":"Servicio de Cardiolog\u00eda, Hospital Universitario de Canarias, 38010 Santa Cruz de Tenerife, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1161\/CIR.0000000000000659","article-title":"Heart Disease and Stroke Statistics-2019 Update: A Report from the American Heart Association","volume":"139","author":"Benjamin","year":"2019","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102934","DOI":"10.1016\/j.dsx.2023.102934","article-title":"Antifibrotic effects of sodium-glucose cotransporter-2 inhibitors: A comprehensive review","volume":"18","author":"Shakour","year":"2023","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11795514231220780","DOI":"10.1177\/11795514231220780","article-title":"Cardiometabolic Risk Factors Associated with Type 2 Diabetes Mellitus: A Mechanistic Insight","volume":"16","author":"Chakraborty","year":"2023","journal-title":"Clin. Med. Insights Endocrinol. Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1136\/heartjnl-2021-320131","article-title":"Prevalence, incidence and survival of heart failure: A systematic review","volume":"108","author":"Johnson","year":"2022","journal-title":"Heart"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41572-019-0106-z","article-title":"Atherosclerosis","volume":"5","author":"Libby","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1235953","DOI":"10.3389\/fcvm.2023.1235953","article-title":"Adipokines in atherosclerosis: Unraveling complex roles","volume":"10","author":"Luo","year":"2023","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejphar.2017.10.052","article-title":"Preface: Pathology and Pharmacology of Atherosclerosis","volume":"816","author":"Foks","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.carrev.2023.07.019","article-title":"Evaluation of stable angina by coronary computed tomographic angiography versus standard of care: A systematic review and meta-analysis","volume":"59","author":"Palicherla","year":"2023","journal-title":"Cardiovasc. Revasc Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/s41581-023-00747-4","article-title":"Diagnosis of cardiovascular disease in patients with chronic kidney disease","volume":"19","author":"Zoccali","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1225178","DOI":"10.3389\/fimmu.2023.1225178","article-title":"The role of macrophage ion channels in the progression of atherosclerosis","volume":"14","author":"Wu","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cmet.2013.11.008","article-title":"Partial and transient reduction of glycolysis by PFKFB3 blockade reduces pathological angiogenesis","volume":"19","author":"Schoors","year":"2014","journal-title":"Cell Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3892\/ijmm.2020.4798","article-title":"Mechanism overview and target mining of atherosclerosis: Endothelial cell injury in atherosclerosis is regulated by glycolysis (Review)","volume":"47","author":"Wang","year":"2021","journal-title":"Int. J. Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4334","DOI":"10.1172\/JCI81676","article-title":"MicroRNA-33-dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis","volume":"125","author":"Ouimet","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1161\/01.ATV.0000064374.15232.C3","article-title":"Lack of interleukin-1beta decreases the severity of atherosclerosis in ApoE-deficient mice","volume":"23","author":"Kirii","year":"2003","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1084\/jem.20150900","article-title":"The glycolytic enzyme PKM2 bridges metabolic and inflammatory dysfunction in coronary artery disease","volume":"213","author":"Shirai","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"120612","DOI":"10.1016\/j.lfs.2022.120612","article-title":"Melatonin: A mitochondrial resident with a diverse skill set","volume":"301","author":"Reiter","year":"2022","journal-title":"Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Fukushi, A., Kim, H.D., Chang, Y.C., and Kim, C.H. (2022). Revisited Metabolic Control and Reprogramming Cancers by Means of the Warburg Effect in Tumor Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231710037"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"279","DOI":"10.3389\/fimmu.2020.00279","article-title":"Lactic Acid: A Novel Signaling Molecule in Early Pregnancy?","volume":"11","author":"Ma","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e12581","DOI":"10.1111\/jpi.12581","article-title":"Melatonin stabilizes rupture-prone vulnerable plaques via regulating macrophage polarization in a nuclear circadian receptor RORalpha-dependent manner","volume":"67","author":"Ding","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1069745","DOI":"10.3389\/fcvm.2023.1069745","article-title":"Novel ultrasound techniques in the identification of vulnerable plaques-an updated review of the literature","volume":"10","author":"Yao","year":"2023","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"107572","DOI":"10.1016\/j.carpath.2023.107572","article-title":"The microenvironment of the atheroma expresses phenotypes of plaque instability","volume":"67","author":"Yan","year":"2023","journal-title":"Cardiovasc. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1097\/RTI.0000000000000711","article-title":"Computed Tomography Assessment of Coronary Atherosclerosis: From Threshold-Based Evaluation to Histologically Validated Plaque Quantification","volume":"38","author":"Schoepf","year":"2023","journal-title":"J. Thorac. Imaging"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Laukaitiene, J., Gujyte, G., and Kadusevicius, E. (2023). Cardiomyocyte Damage: Ferroptosis Relation to Ischemia-Reperfusion Injury and Future Treatment Options. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241612846"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1007\/s00109-023-02346-z","article-title":"Molecular therapy of cardiac ischemia-reperfusion injury based on mitochondria and ferroptosis","volume":"101","author":"Wang","year":"2023","journal-title":"J. Mol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.2174\/1568026623666230825144949","article-title":"The Role of Mettl3 in the Progression of Cardiac Fibrosis","volume":"23","author":"Bolivar","year":"2023","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e24","DOI":"10.15420\/icr.2023.06","article-title":"Revascularisation for Ischaemic Cardiomyopathy","volume":"18","author":"Assar","year":"2023","journal-title":"Interv. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/pin.13202","article-title":"Atherosclerosis: Known and unknown","volume":"72","author":"Fan","year":"2022","journal-title":"Pathol. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1111\/cns.13261","article-title":"Melatonin protects against ischemic stroke by modulating microglia\/macrophage polarization toward anti-inflammatory phenotype through STAT3 pathway","volume":"25","author":"Liu","year":"2019","journal-title":"CNS Neurosci. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1097\/HJH.0000000000001979","article-title":"Melatonin enhances atherosclerotic plaque stability by inducing prolyl-4-hydroxylase alpha1 expression","volume":"37","author":"Li","year":"2019","journal-title":"J. Hypertens."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e31667","DOI":"10.1097\/MD.0000000000031667","article-title":"Costimulatory and coinhibitory molecules of B7-CD28 family in cardiovascular atherosclerosis: A review","volume":"101","author":"Yang","year":"2022","journal-title":"Medicine"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Javanmard, S.H., Heshmat-Ghahdarijani, K., Mirmohammad-Sadeghi, M., Sonbolestan, S.A., and Ziayi, A. (2016). The effect of melatonin on endothelial dysfunction in patient undergoing coronary artery bypass grafting surgery. Adv. Biomed. Res., 5.","DOI":"10.4103\/2277-9175.194801"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Theofilis, P., Vordoni, A., and Kalaitzidis, R.G. (2022). Oxidative Stress Management in Cardiorenal Diseases: Focus on Novel Antidiabetic Agents, Finerenone, and Melatonin. Life, 12.","DOI":"10.3390\/life12101663"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.3892\/etm.2021.10828","article-title":"Melatonin attenuates low shear stress-induced pyroptosis and endothelial cell dysfunction via the RORalpha\/miR-223\/STAT-3 signalling pathway","volume":"22","author":"Yi","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1039\/D2BM01515C","article-title":"NO released via both a Cu-MOF-based donor and surface-catalyzed generation enhances anticoagulation and antibacterial surface effects","volume":"11","author":"Zhang","year":"2022","journal-title":"Biomater. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e12631","DOI":"10.1111\/jpi.12631","article-title":"Melatonin alleviates vascular calcification and ageing through exosomal miR-204\/miR-211 cluster in a paracrine manner","volume":"68","author":"Xu","year":"2020","journal-title":"J. Pineal Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"848","DOI":"10.2174\/1568026623666230116102054","article-title":"The Potential of Melatonin to Treat Atherosclerosis by Targeting Mitochondria","volume":"23","author":"Sun","year":"2023","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/35025203","article-title":"Atherosclerosis","volume":"407","author":"Lusis","year":"2000","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/s41586-021-03392-8","article-title":"The changing landscape of atherosclerosis","volume":"592","author":"Libby","year":"2021","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s13287-022-02832-0","article-title":"Melatonin treatment improves human umbilical cord mesenchymal stem cell therapy in a mouse model of type II diabetes mellitus via the PI3K\/AKT signaling pathway","volume":"13","author":"Aierken","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"362","DOI":"10.5830\/CVJA-2017-018","article-title":"Role of melatonin in glucose uptake by cardiomyocytes from insulin-resistant Wistar rats","volume":"28","author":"Nduhirabandi","year":"2017","journal-title":"Cardiovasc. J. Afr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.ijcard.2014.04.044","article-title":"The potential usefulness of serum melatonin level to predict heart failure in patients with hypertensive cardiomyopathy","volume":"174","author":"Reiter","year":"2014","journal-title":"Int. J. Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"17920","DOI":"10.3390\/ijms151017920","article-title":"Peripheral and central effects of melatonin on blood pressure regulation","volume":"15","author":"Pechanova","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Simko, F., Baka, T., Krajcirovicova, K., Repova, K., Aziriova, S., Zorad, S., Poglitsch, M., Adamcova, M., Reiter, R.J., and Paulis, L. (2018). Effect of Melatonin on the Renin-Angiotensin-Aldosterone System in l-NAME-Induced Hypertension. Molecules, 23.","DOI":"10.3390\/molecules23020265"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1038\/s41440-019-0318-3","article-title":"Melatonin as a rational alternative in the conservative treatment of resistant hypertension","volume":"42","author":"Simko","year":"2019","journal-title":"Hypertens. Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Tiong, Y.L., Ng, K.Y., Koh, R.Y., Ponnudurai, G., and Chye, S.M. (2020). Melatonin inhibits high glucose-induced ox-LDL\/LDL expression and apoptosis in human umbilical endothelial cells. Horm. Mol. Biol. Clin. Investig., 41.","DOI":"10.1515\/hmbci-2020-0009"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.dsx.2014.09.018","article-title":"Type 2 diabetes mellitus: Role of melatonin and oxidative stress","volume":"9","author":"Zephy","year":"2015","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhang, X., Zheng, Y., Wang, Z., Gan, J., Yu, B., Lu, B., and Jiang, X. (2023). Melatonin as a therapeutic agent for alleviating endothelial dysfunction in cardiovascular diseases: Emphasis on oxidative stress. Biomed. Pharmacother., 167.","DOI":"10.1016\/j.biopha.2023.115475"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"362","DOI":"10.32794\/mr11250068","article-title":"Plasticity of glucose metabolism in activated immune cells: Advantages for melatonin inhibition of COVID-19 disease","volume":"3","author":"Reiter","year":"2020","journal-title":"Melatonin Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e12547","DOI":"10.1111\/jpi.12547","article-title":"Melatonin in macrophage biology: Current understanding and future perspectives","volume":"66","author":"Xia","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kumari, A., Syeda, S., Rawat, K., Kumari, R., and Shrivastava, A. (2023). Melatonin modulates L-arginine metabolism in tumor-associated macrophages by targeting arginase 1 in lymphoma. Naunyn Schmiedebergs Arch. Pharmacol.","DOI":"10.1007\/s00210-023-02676-2"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/jpi.12360","article-title":"Melatonin as an antioxidant: Under promises but over delivers","volume":"61","author":"Reiter","year":"2016","journal-title":"J. Pineal Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"110714","DOI":"10.1016\/j.intimp.2023.110714","article-title":"The role of PI3K\/AKT signaling pathway in myocardial ischemia-reperfusion injury","volume":"123","author":"Deng","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"110323","DOI":"10.1016\/j.cellsig.2022.110323","article-title":"Targeting AMPK signaling in ischemic\/reperfusion injury: From molecular mechanism to pharmacological interventions","volume":"94","author":"Paskeh","year":"2022","journal-title":"Cell Signal"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"791036","DOI":"10.3389\/fphys.2021.791036","article-title":"Protective Effect of Melatonin for Renal Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis","volume":"12","author":"Dun","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e13021","DOI":"10.1111\/cpr.13021","article-title":"Melatonin and its protective role in attenuating warm or cold hepatic ischaemia\/reperfusion injury","volume":"54","author":"Hu","year":"2021","journal-title":"Cell Prolif."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"114464","DOI":"10.1016\/j.expneurol.2023.114464","article-title":"Melatonin regulates microglial polarization and protects against ischemic stroke-induced brain injury in mice","volume":"367","author":"Li","year":"2023","journal-title":"Exp. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1600-079X.2011.00931.x","article-title":"Extrapineal melatonin: Analysis of its subcellular distribution and daily fluctuations","volume":"52","author":"Venegas","year":"2012","journal-title":"J. Pineal Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1007\/s00018-017-2609-7","article-title":"Melatonin as a mitochondria-targeted antioxidant: One of evolution\u2019s best ideas","volume":"74","author":"Reiter","year":"2017","journal-title":"Cell Mol. Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Bermudez-Gonzalez, J.L., Sanchez-Quintero, D., Proano-Bernal, L., Santana-Apreza, R., Jimenez-Chavarria, M.A., Luna-Alvarez-Amezquita, J.A., Straface, J.I., Perez-Partida, A.M., Berarducci, J., and Armenta-Moreno, J.I. (2022). Role of the Antioxidant Activity of Melatonin in Myocardial Ischemia-Reperfusion Injury. Antioxidants, 11.","DOI":"10.3390\/antiox11040627"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4610522","DOI":"10.1155\/2022\/4610522","article-title":"Evaluation of Melatonin Therapy in Patients with Myocardial Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis","volume":"2022","author":"Lv","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"888319","DOI":"10.3389\/fcvm.2022.888319","article-title":"Evidence for the Benefits of Melatonin in Cardiovascular Disease","volume":"9","author":"Tobeiha","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"175965","DOI":"10.1016\/j.ejphar.2023.175965","article-title":"Melatonin ameliorates atherosclerosis by suppressing S100a9-mediated vascular inflammation","volume":"957","author":"Chen","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1600-079X.2006.00407.x","article-title":"One molecule, many derivatives: A never-ending interaction of melatonin with reactive oxygen and nitrogen species?","volume":"42","author":"Tan","year":"2007","journal-title":"J. Pineal. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/jpi.12196","article-title":"Melatonin and its metabolites as copper chelating agents and their role in inhibiting oxidative stress: A physicochemical analysis","volume":"58","author":"Galano","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/jpi.12010","article-title":"On the free radical scavenging activities of melatonin\u2019s metabolites, AFMK and AMK","volume":"54","author":"Galano","year":"2013","journal-title":"J. Pineal Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.acthis.2003.10.003","article-title":"Effects of pinealectomy and exogenous melatonin on rat hearts","volume":"106","author":"Mizrak","year":"2004","journal-title":"Acta Histochem."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Taha, A.M., Mahmoud, A.M., Ghonaim, M.M., Kamran, A., AlSamhori, J.F., AlBarakat, M.M., Shrestha, A.B., Jaiswal, V., and Reiter, R.J. (2023). Melatonin as a potential treatment for septic cardiomyopathy. Biomed. Pharmacother., 166.","DOI":"10.1016\/j.biopha.2023.115305"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"703175","DOI":"10.1155\/2014\/703175","article-title":"Hypertension and cardiovascular remodelling in rats exposed to continuous light: Protection by ACE-inhibition and melatonin","volume":"2014","author":"Simko","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/jpi.12190","article-title":"Cardioprotective effects of melatonin against myocardial injuries induced by chronic intermittent hypoxia in rats","volume":"58","author":"Yeung","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e12829","DOI":"10.1111\/jpi.12829","article-title":"Melatonin improves cardiac remodeling and brain-heart sympathetic hyperactivation aggravated by light disruption after myocardial infarction","volume":"73","author":"Jiao","year":"2022","journal-title":"J. Pineal Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5811","DOI":"10.1007\/s11033-021-06526-3","article-title":"Melatonin ameliorates cardiac remodelling in fructose-induced metabolic syndrome rat model by using genes encoding cardiac potassium ion channels","volume":"48","author":"Ovali","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s10557-020-07052-3","article-title":"Clinical Application of Melatonin in the Treatment of Cardiovascular Diseases: Current Evidence and New Insights into the Cardioprotective and Cardiotherapeutic Properties","volume":"36","author":"Pourhanifeh","year":"2022","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Dominguez-Rodriguez, A., Hernandez-Vaquero, D., Abreu-Gonzalez, P., Baez-Ferrer, N., Diaz, R., Avanzas, P., Simko, F., Dominguez-Gonzalez, V., Sharma, R., and Reiter, R.J. (2022). Early Treatment of Acute Myocardial Infarction with Melatonin: Effects on MMP-9 and Adverse Cardiac Events. J. Clin. Med., 11.","DOI":"10.3390\/jcm11071909"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Triposkiadis, F., Sarafidis, P., Briasoulis, A., Magouliotis, D.E., Athanasiou, T., Skoularigis, J., and Xanthopoulos, A. (2023). Hypertensive Heart Failure. J. Clin. Med., 12.","DOI":"10.3390\/jcm12155090"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s41569-022-00806-6","article-title":"Regression of cardiac hypertrophy in health and disease: Mechanisms and therapeutic potential","volume":"20","author":"Martin","year":"2023","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Nemtsova, V., Burkard, T., and Vischer, A.S. (2023). Hypertensive Heart Disease: A Narrative Review Series-Part 2: Macrostructural and Functional Abnormalities. J. Clin. Med., 12.","DOI":"10.3390\/jcm12175723"},{"key":"ref_77","first-page":"507","article-title":"Left ventricular hypertrophy regression as a process with variable biological implications","volume":"12","author":"Simko","year":"1996","journal-title":"Can. J. Cardiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1097\/01.hjh.0000388489.28213.08","article-title":"Continuous light and L-NAME-induced left ventricular remodelling: Different protection with melatonin and captopril","volume":"28","author":"Simko","year":"2010","journal-title":"J. Hypertens."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.cellsig.2018.03.012","article-title":"Melatonin therapy for diabetic cardiomyopathy: A mechanism involving Syk-mitochondrial complex I-SERCA pathway","volume":"47","author":"Zhou","year":"2018","journal-title":"Cell Signal"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1097\/01.hjh.0000358831.33558.97","article-title":"Melatonin prevents fibrosis but not hypertrophy development in the left ventricle of NG-nitro-L-arginine-methyl ester hypertensive rats","volume":"27","author":"Paulis","year":"2009","journal-title":"J. Hypertens. Suppl."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Simko, F., Pechanova, O., Repova, K., Aziriova, S., Krajcirovicova, K., Celec, P., Tothova, L., Vrankova, S., Balazova, L., and Zorad, S. (2017). Lactacystin-Induced Model of Hypertension in Rats: Effects of Melatonin and Captopril. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18081612"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1097\/01.hjh.0000358830.95439.e8","article-title":"Effect of melatonin, captopril, spironolactone and simvastatin on blood pressure and left ventricular remodelling in spontaneously hypertensive rats","volume":"27","author":"Simko","year":"2009","journal-title":"J. Hypertens. Suppl."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1097\/01.hjh.0000388490.28213.de","article-title":"Melatonin improves the restoration of endothelium-derived constricting factor signalling and inner diameter in the rat femoral artery after cessation of L-NAME treatment","volume":"28","author":"Paulis","year":"2010","journal-title":"J. Hypertens."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s11010-016-2808-9","article-title":"Melatonin attenuates angiotensin II-induced cardiomyocyte hypertrophy through the CyPA\/CD147 signaling pathway","volume":"422","author":"Su","year":"2016","journal-title":"Mol. Cell Biochem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"493","DOI":"10.18632\/aging.202159","article-title":"Melatonin alleviates angiotensin-II-induced cardiac hypertrophy via activating MICU1 pathway","volume":"13","author":"Yang","year":"2020","journal-title":"Aging"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.arcmed.2017.12.003","article-title":"Correlations of Serum Cyclophilin A and Melatonin Concentrations with Hypertension-induced Left Ventricular Hypertrophy","volume":"48","author":"Su","year":"2017","journal-title":"Arch. Med. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e15625","DOI":"10.1016\/j.heliyon.2023.e15625","article-title":"Spleen tyrosine kinase (SYK) signals are implicated in cardio-cerebrovascular diseases","volume":"9","author":"Li","year":"2023","journal-title":"Heliyon"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1185261","DOI":"10.3389\/fcvm.2023.1185261","article-title":"Targeting calcium regulators as therapy for heart failure: Focus on the sarcoplasmic reticulum Ca-ATPase pump","volume":"10","author":"Kho","year":"2023","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Kaczmarek, A., Wronska, A.K., and Bogus, M.I. (2023). The Changes in Mitochondrial Morphology and Physiology Accompanying Apoptosis in Galleria mellonella (Lepidoptera) Immunocompetent Cells during Conidiobolus coronatus (Entomophthorales) Infection. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241210169"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3892\/mmr.2020.11746","article-title":"Intermedin protects thapsigargin-induced endoplasmic reticulum stress in cardiomyocytes by modulating protein kinase A and sarco\/endoplasmic reticulum Ca2+-ATPase","volume":"23","author":"Li","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e12418","DOI":"10.1111\/jpi.12418","article-title":"Melatonin protects against diabetic cardiomyopathy through Mst1\/Sirt3 signaling","volume":"63","author":"Zhang","year":"2017","journal-title":"J. Pineal Res."},{"key":"ref_92","first-page":"374","article-title":"Melatonin ameliorates myocardial apoptosis by suppressing endoplasmic reticulum stress in rats with long-term diabetic cardiomyopathy","volume":"17","author":"Xiong","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"47","DOI":"10.14715\/cmb\/2018.64.14.8","article-title":"Melatonin protects against streptozotocin-induced diabetic cardiomyopathy by the phosphorylation of vascular endothelial growth factor-A (VEGF-A)","volume":"64","author":"Guntekin","year":"2018","journal-title":"Cell. Mol. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"5132","DOI":"10.1111\/jcmm.13802","article-title":"Melatonin activates Parkin translocation and rescues the impaired mitophagy activity of diabetic cardiomyopathy through Mst1 inhibition","volume":"22","author":"Wang","year":"2018","journal-title":"J. Cell Mol. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e00904","DOI":"10.1002\/prp2.904","article-title":"New insights into the role of melatonin in diabetic cardiomyopathy","volume":"10","author":"Huang","year":"2022","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Tang, H., Zhong, H., Liu, W., Wang, Y., Wang, Y., Wang, L., Tang, S., and Zhu, H. (2022). Melatonin Alleviates Hyperglycemia-Induced Cardiomyocyte Apoptosis via Regulation of Long Non-Coding RNA H19\/miR-29c\/MAPK Axis in Diabetic Cardiomyopathy. Pharmaceuticals, 15.","DOI":"10.3390\/ph15070821"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"8882130","DOI":"10.1155\/2021\/9793010","article-title":"Melatonin Attenuates Diabetic Myocardial Microvascular Injury through Activating the AMPK\/SIRT1 Signaling Pathway","volume":"2021","author":"Wang","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"5282","DOI":"10.1096\/fj.201902692R","article-title":"Melatonin alleviates cardiac fibrosis via inhibiting lncRNA MALAT1\/miR-141-mediated NLRP3 inflammasome and TGF-beta1\/Smads signaling in diabetic cardiomyopathy","volume":"34","author":"Che","year":"2020","journal-title":"FASEB J."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Kim, K.W., Ivanov, S., and Williams, J.W. (2020). Monocyte Recruitment, Specification, and Function in Atherosclerosis. Cells, 10.","DOI":"10.3390\/cells10010015"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"10990","DOI":"10.1002\/jcp.27910","article-title":"Galectin-3 exacerbates ox-LDL-mediated endothelial injury by inducing inflammation via integrin beta1-RhoA-JNK signaling activation","volume":"234","author":"Chen","year":"2019","journal-title":"J. Cell Physiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e12855","DOI":"10.1111\/jpi.12855","article-title":"Melatonin inhibits atherosclerosis progression via galectin-3 downregulation to enhance autophagy and inhibit inflammation","volume":"74","author":"Wang","year":"2023","journal-title":"J. Pineal Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e12667","DOI":"10.1111\/jpi.12667","article-title":"Melatonin prevents neuroinflammation and relieves depression by attenuating autophagy impairment through FOXO3a regulation","volume":"69","author":"Ali","year":"2020","journal-title":"J. Pineal Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"7687083","DOI":"10.1155\/2018\/7687083","article-title":"Defective Autophagy in Atherosclerosis: To Die or to Senesce?","volume":"2018","author":"Grootaert","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Milliken, A.S., Kulkarni, C.A., and Brookes, P.S. (2020). Acid enhancement of ROS generation by complex-I reverse electron transport is balanced by acid inhibition of complex-II: Relevance for tissue reperfusion injury. Redox Biol., 37.","DOI":"10.1016\/j.redox.2020.101733"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1749-6632.2010.05634.x","article-title":"Oxidative stress caused by mitochondrial calcium overload","volume":"1201","author":"Peng","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1600-079X.2004.00140.x","article-title":"Visualization of the antioxidative effects of melatonin at the mitochondrial level during oxidative stress-induced apoptosis of rat brain astrocytes","volume":"37","author":"Jou","year":"2004","journal-title":"J. Pineal Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"E7997","DOI":"10.1073\/pnas.1705768114","article-title":"Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release","volume":"114","author":"Suofu","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1114231","DOI":"10.3389\/fphys.2023.1114231","article-title":"Mitochondria: It is all about energy","volume":"14","author":"Casanova","year":"2023","journal-title":"Front. Physiol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Galano, A., Tan, D.X., and Reiter, R.J. (2018). Melatonin: A Versatile Protector against Oxidative DNA Damage. Molecules, 23.","DOI":"10.3390\/molecules23030530"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2174\/156802611794863517","article-title":"Melatonin-mitochondria interplay in health and disease","volume":"11","author":"Lopez","year":"2011","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1016\/S0140-6736(95)92600-3","article-title":"Impaired nocturnal secretion of melatonin in coronary heart disease","volume":"345","author":"Brugger","year":"1995","journal-title":"Lancet"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e12564","DOI":"10.1111\/jpi.12564","article-title":"Plasma levels of melatonin in dilated cardiomyopathy","volume":"66","author":"Misaka","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1161\/ATVBAHA.123.319026","article-title":"Sleep Deprivation Promotes Endothelial Inflammation and Atherogenesis by Reducing Exosomal miR-182-5p","volume":"43","author":"Li","year":"2023","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.amjcard.2017.05.018","article-title":"Usefulness of Early Treatment with Melatonin to Reduce Infarct Size in Patients with ST-Segment Elevation Myocardial Infarction Receiving Percutaneous Coronary Intervention (from the Melatonin Adjunct in the Acute Myocardial Infarction Treated with Angioplasty Trial)","volume":"120","author":"Piccolo","year":"2017","journal-title":"Am. J. Cardiol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"173506","DOI":"10.1016\/j.ejphar.2020.173506","article-title":"Melatonin as a protective agent in cardiac ischemia-reperfusion injury: Vision\/Illusion?","volume":"885","author":"Randhawa","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/jpi.12175","article-title":"A review of melatonin as a suitable antioxidant against myocardial ischemia-reperfusion injury and clinical heart diseases","volume":"57","author":"Yang","year":"2014","journal-title":"J. Pineal Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.ijcard.2016.07.108","article-title":"Melatonin effects on myocardial ischemia-reperfusion injury: Impact on the outcome in patients undergoing coronary artery bypass grafting surgery","volume":"221","author":"Dwaich","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1007\/s12265-017-9768-7","article-title":"Effect of Intracoronary and Intravenous Melatonin on Myocardial Salvage Index in Patients with ST-Elevation Myocardial Infarction: A Randomized Placebo Controlled Trial","volume":"10","author":"Ekeloef","year":"2017","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_119","first-page":"851","article-title":"Effect of Melatonin on Cardiac Injury after Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial","volume":"14","author":"Ghaeli","year":"2015","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/jpi.12138","article-title":"Melatonin reduces cardiac morbidity and markers of myocardial ischemia after elective abdominal aortic aneurism repair: A randomized, placebo-controlled, clinical trial","volume":"57","author":"Gogenur","year":"2014","journal-title":"J. Pineal Res."},{"key":"ref_121","first-page":"2","article-title":"Melatonin as an anti-cancer agent: Time of administration may be critical","volume":"4","author":"Reiter","year":"2023","journal-title":"Adv. Can. Res. Clin. Imag."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Cardinali, D.P. (2023). Melatonin as a chronobiotic\/cytoprotective agent in bone. Doses involved. J. Pineal Res., e12931.","DOI":"10.1111\/jpi.12931"},{"key":"ref_123","unstructured":"U.S. Food & Drug Administration (2005). Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers, U.S. Food & Drug Administration."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Ozon, E.A., Iuga, I.D.M., Mititelu, M., Musuc, A.M., Manolescu, B.N., Petrescu, S., Cusu, J.P., Rusu, A., Surdu, V.A., and Oprea, E. (2023). Pharmacotechnical, Physico-Chemical, and Antioxidant Evaluation of Newly Developed Capsule Formulations. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411426"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Sun, Y., Chen, J., Shi, X., Li, Z., Wan, L., Yan, H., Chen, Y., Wang, J., Wang, J., and Zou, L. (2023). Safety and efficacy of melatonin supplementation as an add-on treatment for infantile epileptic spasms syndrome: A randomized, placebo-controlled, double-blind trial. J. Pineal Res., e12922.","DOI":"10.1111\/jpi.12922"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Loh, D., and Reiter, R.J. (2021). Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders. Antioxidants, 10.","DOI":"10.3390\/antiox10091483"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/1\/88\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:40:24Z","timestamp":1760103624000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/1\/88"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,5]]},"references-count":126,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["life14010088"],"URL":"https:\/\/doi.org\/10.3390\/life14010088","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,5]]}}}