{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T18:36:55Z","timestamp":1774550215127,"version":"3.50.1"},"reference-count":56,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T00:00:00Z","timestamp":1591660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["NET-2011-02347173"],"award-info":[{"award-number":["NET-2011-02347173"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the myocardium associated to mutations in sarcomeric genes, but the link between genotype and phenotype remains poorly understood. Magnetic resonance spectroscopy studies have demonstrated impaired cardiac energetics in patients with HCM, and altered mitochondria were described in biopsies, but little is known about possible perturbations of mitochondrial function and adenosine triphosphate (ATP) production\/consumption. The aim of this study was to investigate possible abnormalities in mitochondrial enzymes generating\/scavenging reactive oxygen species, and changes in the Ca2+-activated ATPases in myocardial tissue from patients with obstructive HCM undergoing surgical myectomy compared to unused donor hearts (CTRL). Methods and Results: Both the amount and activity of mitochondrial Complex I (nicotinamide adenine dinucleotide -reduced form, NADH, dehydrogenase) were upregulated in HCM vs. CTRL, whilst the activity of Complex V (ATP synthase) was not reduced and ATP levels were significantly higher in HCM vs. CTRL. Antioxidant Mn-activated superoxide dismutase (SOD2) and (m)-aconitase activities were increased in HCM vs. CTRL. The Cu\/Zn-activated superoxide dismutase (SOD1) amount and mtDNA copy number were unaltered in HCM. Total Ca2+-activated ATPase activity and absolute amount were not different HCM vs. CTRL, but the ratio between ATPase sarcoplasmic\/endoplasmic reticulum Ca2+ transporting type 2 (ATP2A2) and type 1 (ATP2A1), ATP2A2\/ATP2A1, was increased in HCM in favor of the slow isoform (ATP2A2). Conclusion: HCM is characterized by mitochondrial Complex I hyperactivity and preserved Ca2+-activated ATPase activity with a partial switch towards slow ATP2A2. This data may give insight into the abnormal cellular energetics observed in HCM cardiomyopathy but other studies would need to be performed to confirm the observations described here.<\/jats:p>","DOI":"10.3390\/jcm9061799","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T08:49:11Z","timestamp":1591692551000},"page":"1799","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Mitochondrial Energetics and Ca2+-Activated ATPase in Obstructive Hypertrophic Cardiomyopathy"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8198-5264","authenticated-orcid":false,"given":"Maria","family":"Lombardi","sequence":"first","affiliation":[{"name":"Cardiovascular Research Center, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Lazzeroni","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annalinda","family":"Pisano","sequence":"additional","affiliation":[{"name":"Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome and Policlinico Umberto I, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Girolami","sequence":"additional","affiliation":[{"name":"Cardiology Unit, Meyer Children\u2019s Hospital, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ottavio","family":"Alfieri","sequence":"additional","affiliation":[{"name":"Cardiac Surgery Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"La Canna","sequence":"additional","affiliation":[{"name":"Applied Diagnostic Echocardiography Unit, Cardiovascular Department, Humanitas Clinical and Research Hospital, 20089 Rozzano-Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6959-691X","authenticated-orcid":false,"given":"Giulia","family":"d\u2019Amati","sequence":"additional","affiliation":[{"name":"Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome and Policlinico Umberto I, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iacopo","family":"Olivotto","sequence":"additional","affiliation":[{"name":"Cardiomyopathy Unit, Careggi University Hospital, 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ornella E.","family":"Rimoldi","sequence":"additional","affiliation":[{"name":"Institute of Molecular Bioimaging and Physiology, National Research Council (IBFM-CNR), 20090 Segrate-Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5155-6426","authenticated-orcid":false,"given":"Chiara","family":"Foglieni","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo G.","family":"Camici","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Faculty of Medicine and Surgery, Vita-Salute University, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/cvr\/cvv025","article-title":"Genetic advances in sarcomeric cardiomyopathies: State of the art","volume":"105","author":"Ho","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hayashi, T. (2020). Hypertrophic Cardiomyopathy: Diverse Pathophysiology Revealed by Genetic Research, Toward Future Therapy. Keio J. Med.","DOI":"10.2302\/kjm.2019-0012-OA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1161\/CIRCRESAHA.117.311059","article-title":"Hypertrophic Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy","volume":"121","author":"Marian","year":"2017","journal-title":"Circ. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1093\/cvr\/cvy147","article-title":"Metabolic changes in hypertrophic cardiomyopathies: Scientific update from the Working Group of Myocardial Function of the European Society of Cardiology","volume":"114","author":"Tocchetti","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.amjcard.2013.05.017","article-title":"Creatine kinase adenosine triphosphate and phosphocreatine energy supply in a single kindred of patients with hypertrophic cardiomyopathy","volume":"112","author":"Abraham","year":"2013","journal-title":"Am. J. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1016\/S0735-1097(02)03009-7","article-title":"Hypertrophic cardiomyopathy due to sarcomeric gene mutations is characterized by impaired energy metabolism irrespective of the degree of hypertrophy","volume":"41","author":"Crilley","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1161\/01.CIR.97.25.2536","article-title":"31P NMR spectroscopy detects metabolic abnormalities in asymptomatic patients with hypertrophic cardiomyopathy","volume":"97","author":"Jung","year":"1998","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nrcardio.2016.98","article-title":"Myocardial energy depletion and dynamic systolic dysfunction in hypertrophic cardiomyopathy","volume":"13","author":"Ormerod","year":"2016","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_9","first-page":"2965","article-title":"Interactions between sarco-endoplasmic reticulum and mitochondria in cardiac and skeletal muscle\u2014Pivotal roles in Ca(2)(+) and reactive oxygen species signaling","volume":"126","author":"Eisner","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Saha, B., Johnstone, V., Viola, H., Filipovska, A., and Hool, L. (2017, January 10\u201313). Characterising Mitochondrial Morphology and Signalling in Familial Hypertrophic Cardiomyopathy. Proceedings of the 65th Cardiac Society of Australia and New Zealand Annual Scientific Meeting and the International Society for Heart Research Australasian Section Annual Scientific Meeting, Perth, Australia.","DOI":"10.1016\/j.hlc.2017.06.140"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1093\/eurheartj\/ehp184","article-title":"Relation of functional and morphological changes in mitochondria to myocardial contractile and relaxation reserves in asymptomatic to mildly symptomatic patients with hypertrophic cardiomyopathy","volume":"30","author":"Unno","year":"2009","journal-title":"Eur. Heart J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.cardfail.2004.05.005","article-title":"Relationship between oxidative stress and systolic dysfunction in patients with hypertrophic cardiomyopathy","volume":"11","author":"Nakamura","year":"2005","journal-title":"J. Card. Fail."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"309","DOI":"10.3389\/fphys.2014.00309","article-title":"Hypertrophic cardiomyopathy: A heart in need of an energy bar?","volume":"5","author":"Vakrou","year":"2014","journal-title":"Front. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"H575","DOI":"10.1152\/ajpheart.00619.2002","article-title":"Alterations in mitochondrial function in a mouse model of hypertrophic cardiomyopathy","volume":"284","author":"Lucas","year":"2003","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e94493","DOI":"10.1172\/jci.insight.94493","article-title":"Allele-specific differences in transcriptome, miRNome, and mitochondrial function in two hypertrophic cardiomyopathy mouse models","volume":"3","author":"Vakrou","year":"2018","journal-title":"JCI Insight"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.1093\/eurheartj\/ehu284","article-title":"2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: The Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC)","volume":"35","author":"Elliott","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1161\/CIRCULATIONAHA.106.644682","article-title":"Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract obstruction","volume":"114","author":"Maron","year":"2006","journal-title":"Circulation"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1093\/eurheartj\/ehy339","article-title":"2018 ESC\/ESH Guidelines for the management of arterial hypertension","volume":"39","author":"Williams","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1111\/j.1365-2559.2004.01835.x","article-title":"The pathology of hypertrophic cardiomyopathy","volume":"44","author":"Hughes","year":"2004","journal-title":"Histopathology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1038\/gim.2017.258","article-title":"CardioClassifier: Disease- and gene-specific computational decision support for clinical genome interpretation","volume":"20","author":"Whiffin","year":"2018","journal-title":"Genet. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.ajhg.2017.01.004","article-title":"InterVar: Clinical Interpretation of Genetic Variants by the 2015 ACMG-AMP Guidelines","volume":"100","author":"Li","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/1475-2891-10-77","article-title":"Mn bioavailability by polarized Caco-2 cells: Comparison between Mn gluconate and Mn oxyprolinate","volume":"10","author":"Foglieni","year":"2011","journal-title":"Nutr. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/BF00499665","article-title":"The effect of temperature on the pH stability of myosin ATPase as demonstrated histochemically","volume":"38","author":"Khan","year":"1974","journal-title":"Histochemie"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.carpath.2015.09.009","article-title":"Impaired mitochondrial biogenesis is a common feature to myocardial hypertrophy and end-stage ischemic heart failure","volume":"25","author":"Pisano","year":"2016","journal-title":"Cardiovasc. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4872","DOI":"10.1038\/s41598-017-05137-y","article-title":"P2X7 receptor antagonism modulates IL-1beta and MMP9 in human atherosclerotic vessels","volume":"7","author":"Lombardi","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/0014-5793(77)80820-X","article-title":"Biochemical and histochemical evidence for stimulation of myosin ATPase activity in thyrotoxic rabbit heart","volume":"79","author":"Morkin","year":"1977","journal-title":"FEBS Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1161\/01.RES.51.6.802","article-title":"Histochemical detection of specific isozymes of myosin in rat ventricular cells","volume":"51","author":"Weisberg","year":"1982","journal-title":"Circ. Res."},{"key":"ref_29","first-page":"131","article-title":"Analysis of skeletal and cardiac muscle from desmin knock-out and normal mice by high resolution separation of myosin heavy-chain isoforms","volume":"88","author":"Agbulut","year":"1996","journal-title":"Biol. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/S0021-9258(18)66180-0","article-title":"A microcolorimetric method for the determination of inorganic phosphorus","volume":"202","author":"Taussky","year":"1953","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1161\/01.RES.19.3.611","article-title":"Adenosinetriphosphatase activity of cardiac myosin. Comparison of the enzymatic activities and activation by actin of dog cardiac, rabbit cardiac, rabbit white skeletal and rabbit red skeletal muscle myosins","volume":"19","author":"Katz","year":"1966","journal-title":"Circ. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1093\/ehjci\/jes242","article-title":"Coronary microvascular function, myocardial metabolism, and energetics in hypertrophic cardiomyopathy: Insights from positron emission tomography","volume":"14","author":"Timmer","year":"2013","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1056\/NEJMra0902923","article-title":"Inherited cardiomyopathies","volume":"364","author":"Watkins","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1161\/CIRCULATIONAHA.112.134932","article-title":"Late sodium current inhibition reverses electromechanical dysfunction in human hypertrophic cardiomyopathy","volume":"127","author":"Coppini","year":"2013","journal-title":"Circulation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/eurheartj\/ehv120","article-title":"Exacerbation of cardiac energetic impairment during exercise in hypertrophic cardiomyopathy: A potential mechanism for diastolic dysfunction","volume":"36","author":"Dass","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"H1237","DOI":"10.1152\/ajpheart.00727.2014","article-title":"Impaired cardiac mitochondrial oxidative phosphorylation and enhanced mitochondrial oxidative stress in feline hypertrophic cardiomyopathy","volume":"308","author":"Christiansen","year":"2015","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"H1720","DOI":"10.1152\/ajpheart.00339.2015","article-title":"N-acetylcysteine reverses diastolic dysfunction and hypertrophy in familial hypertrophic cardiomyopathy","volume":"309","author":"Wilder","year":"2015","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14064","DOI":"10.1074\/jbc.275.19.14064","article-title":"Mitochondrial aconitase is a source of hydroxyl radical. An electron spin resonance investigation","volume":"275","author":"Kalyanaraman","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1126\/science.1106391","article-title":"Aconitase couples metabolic regulation to mitochondrial DNA maintenance","volume":"307","author":"Chen","year":"2005","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1161\/CIRCRESAHA.114.300559","article-title":"Cardiac mitochondria and reactive oxygen species generation","volume":"114","author":"Chen","year":"2014","journal-title":"Circ. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1006\/jmcc.1999.1061","article-title":"Antioxidative enzymes in human hearts with idiopathic dilated cardiomyopathy","volume":"32","author":"Baumer","year":"2000","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1097\/FJC.0000000000000210","article-title":"Mitochondrial ATP-sensitive potassium channel opening inhibits isoproterenol-induced cardiac hypertrophy by preventing oxidative damage","volume":"65","author":"Martins","year":"2015","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/1423-0127-21-57","article-title":"Downregulation of Sirt1 as aging change in advanced heart failure","volume":"21","author":"Lu","year":"2014","journal-title":"J. Biomed. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"E449","DOI":"10.1152\/ajpendo.00127.2016","article-title":"Posttranslational modifications and dysfunction of mitochondrial enzymes in human heart failure","volume":"311","author":"Sheeran","year":"2016","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1006\/jmcc.2000.1266","article-title":"Abnormal mitochondrial respiration in failed human myocardium","volume":"32","author":"Sharov","year":"2000","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.cardfail.2005.01.007","article-title":"Increased reactive oxygen species production and functional alterations in antioxidant enzymes in human failing myocardium","volume":"11","author":"Sam","year":"2005","journal-title":"J. Card. Fail."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1093\/nar\/gkp100","article-title":"Oxidative stress induces degradation of mitochondrial DNA","volume":"37","author":"Shokolenko","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.jchf.2017.09.011","article-title":"Clinical Spectrum and Management of Heart Failure in Hypertrophic Cardiomyopathy","volume":"6","author":"Maron","year":"2018","journal-title":"JACC Heart Fail."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/S0735-1097(02)02160-5","article-title":"Absolute concentrations of high-energy phosphate metabolites in normal, hypertrophied, and failing human myocardium measured noninvasively with (31)P-SLOOP magnetic resonance spectroscopy","volume":"40","author":"Beer","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_50","first-page":"H265","article-title":"Relation between phosphate metabolites and oxygen consumption of heart in vivo","volume":"256","author":"Katz","year":"1989","journal-title":"Am. J. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1091\/mbc.e08-07-0783","article-title":"Mitochondria are linked to calcium stores in striated muscle by developmentally regulated tethering structures","volume":"20","author":"Boncompagni","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1161\/hh1401.093440","article-title":"Energetic crosstalk between organelles: Architectural integration of energy production and utilization","volume":"89","author":"Kaasik","year":"2001","journal-title":"Circ. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1517\/14712590903321462","article-title":"Sarcoplasmic reticulum Ca(2+) ATPase as a therapeutic target for heart failure","volume":"10","author":"Lipskaia","year":"2010","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5622","DOI":"10.1073\/pnas.0305778101","article-title":"Abrogation of ventricular arrhythmias in a model of ischemia and reperfusion by targeting myocardial calcium cycling","volume":"101","author":"Lebeche","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1161\/01.CIR.101.1.33","article-title":"Gene expression of antioxidative enzymes in the human heart: Increased expression of catalase in the end-stage failing heart","volume":"101","author":"Dieterich","year":"2000","journal-title":"Circulation"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0168-9525(03)00081-7","article-title":"Hypertrophic cardiomyopathy: A paradigm for myocardial energy depletion","volume":"19","author":"Ashrafian","year":"2003","journal-title":"Trends Genet."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/6\/1799\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:37:07Z","timestamp":1760175427000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/6\/1799"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,9]]},"references-count":56,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["jcm9061799"],"URL":"https:\/\/doi.org\/10.3390\/jcm9061799","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,9]]}}}