{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:59:23Z","timestamp":1760144363923,"version":"build-2065373602"},"reference-count":67,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T00:00:00Z","timestamp":1712966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Myocardial hypertrophy is the most common condition that accompanies heart development in children. Transcriptional gene expression regulating pathways play a critical role both in cardiac embryogenesis and in the pathogenesis of congenital hypertrophic cardiomyopathy, neonatal posthypoxic myocardial hypertrophy, and congenital heart diseases. This paper describes the state of cardiac gene expression and potential pharmacological modulators at different transcriptional levels. An experimental model of perinatal cardiac hypoxia showed the downregulated expression of genes responsible for cardiac muscle integrity and overexpressed genes associated with energy metabolism and apoptosis, which may provide a basis for a therapeutic approach. Current evidence suggests that RNA drugs, theaflavin, neuraminidase, proton pumps, and histone deacetylase inhibitors are promising pharmacological agents in progressive cardiac hypertrophy. The different points of application of the above drugs make combined use possible, potentiating the effects of inhibition in specific signaling pathways. The special role of N-acetyl cysteine in both the inhibition of several signaling pathways and the reduction of oxidative stress was emphasized.<\/jats:p>","DOI":"10.3390\/biom14040477","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T11:53:53Z","timestamp":1713182033000},"page":"477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined Pharmacological Modulation of Translational and Transcriptional Activity Signaling Pathways as a Promising Therapeutic Approach in Children with Myocardial Changes"],"prefix":"10.3390","volume":"14","author":[{"given":"Andrii","family":"Kamenshchyk","sequence":"first","affiliation":[{"name":"Department of Hospital Pediatrics, Zaporizhzhya State Medical and Pharmaceutical University, 69035 Zaporizhzhya, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1273-5314","authenticated-orcid":false,"given":"Igor","family":"Belenichev","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Zaporizhzhya State Medical and Pharmaceutical University, 69035 Zaporizhzhya, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5088-3791","authenticated-orcid":false,"given":"Valentyn","family":"Oksenych","sequence":"additional","affiliation":[{"name":"Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3141-4436","authenticated-orcid":false,"given":"Oleksandr","family":"Kamyshnyi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Virology and Immunology, I. Horbachevsky Ternopil State Medical University, 46001 Ternopil, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,13]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Regulatory T Cells in Pathological Cardiac Hypertrophy: Mechanisms and Therapeutic Potential","volume":"37","author":"Liu","year":"2023","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.jacc.2017.12.008","article-title":"A Surprising Noncanonical Role for Calcineurin in Pressure-Induced Cardiac Hypertrophy","volume":"71","author":"Shaw","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e2199","DOI":"10.1038\/cddis.2016.97","article-title":"Cell cycle and apoptosis regulation by NFAT transcription factors: New roles for an old player","volume":"7","author":"Mognol","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1161\/CIRCRESAHA.119.315992","article-title":"Nfatc1 Promotes Interstitial Cell Formation During Cardiac Valve Development in Zebrafish","volume":"126","author":"Gunawan","year":"2020","journal-title":"Circ. Res."},{"key":"ref_5","first-page":"473","article-title":"Endocardial-to-mesenchymal transformation and mesenchymal cell colonization at the onset of human cardiac valve development","volume":"143","author":"Monaghan","year":"2016","journal-title":"Development"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kamenshchyk, A., Gonchar, M., Oksenych, V., and Kamyshnyi, A. (2023). Association of Myocardial Changes and Gene Expression of the NFATC1 and NFATC4-Calcineurin Signaling Pathway in Children with Bicuspid Aortic Valve. Children, 10.","DOI":"10.20944\/preprints202307.1504.v1"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41569-018-0007-y","article-title":"Mechanisms of physiological and pathological cardiac hypertrophy","volume":"15","author":"Nakamura","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1093\/cvr\/cvaa233","article-title":"Gene expression profiling of hypertrophic cardiomyocytes identifies new players in pathological remodelling","volume":"117","author":"Demkes","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"110134","DOI":"10.1016\/j.cellsig.2021.110134","article-title":"Calcineurin in the heart: New horizons for an old friend","volume":"87","author":"Chaklader","year":"2021","journal-title":"Cell Signal"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bazgir, F., Nau, J., Nakhaei-Rad, S., Amin, E., Wolf, M.J., Saucerman, J.J., Lorenz, K., and Ahmadian, M.R. (2023). The Microenvironment of the Pathogenesis of Cardiac Hypertrophy. Cells, 12.","DOI":"10.3390\/cells12131780"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3462","DOI":"10.1093\/eurheartj\/ehaa519","article-title":"Targeting muscle-enriched long non-coding RNA H19 reverses pathological cardiac hypertrophy","volume":"41","author":"Viereck","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/978-981-15-1671-9_13","article-title":"Non-coding RNAs and Pathological Cardiac Hypertrophy","volume":"1229","author":"He","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e016419","DOI":"10.1161\/JAHA.120.016419","article-title":"NULP1 Alleviates Cardiac Hypertrophy by Suppressing NFAT3 Transcriptional Activity","volume":"9","author":"Zhang","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhou, H., Xia, C., Yang, Y., Warusawitharana, H.K., Liu, X., and Tu, Y. (2022). The Prevention Role of Theaflavin-3,3\u2019-digallate in Angiotensin II Induced Pathological Cardiac Hypertrophy via CaN-NFAT Signal Pathway. Nutrients, 14.","DOI":"10.3390\/nu14071391"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"931475","DOI":"10.3389\/fcvm.2022.931475","article-title":"Mechanism of histone deacetylases in cardiac hypertrophy and its therapeutic inhibitors","volume":"9","author":"Han","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"C338","DOI":"10.1152\/ajpcell.00409.2021","article-title":"Histone deacetylase inhibitors (HDACi) increase expression of KCa2.3 (SK3) in primary microvascular endothelial cells","volume":"322","author":"Balut","year":"2022","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1007\/s12272-020-01297-0","article-title":"Therapeutic effects of histone deacetylase inhibitors on heart disease","volume":"43","author":"Chun","year":"2020","journal-title":"Arch. Pharm. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1007\/s00395-020-00821-z","article-title":"Neuraminidase-1 promotes heart failure after ischemia\/reperfusion injury by affecting cardiomyocytes and invading monocytes\/macrophages","volume":"115","author":"Heimerl","year":"2020","journal-title":"Basic. Res. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3770","DOI":"10.1093\/eurheartj\/ehab347","article-title":"Neuraminidase 1 is a driver of experimental cardiac hypertrophy","volume":"42","author":"Chen","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1093\/cvr\/cvz016","article-title":"Lansoprazole alleviates pressure overload-induced cardiac hypertrophy and heart failure in mice by blocking the activation of beta-catenin","volume":"116","author":"Lin","year":"2020","journal-title":"Cardiovasc. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/pr.2017.96","article-title":"Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm","volume":"82","author":"Aye","year":"2017","journal-title":"Pediatr. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"401323","DOI":"10.1155\/2010\/401323","article-title":"Causes and mechanisms of intrauterine hypoxia and its impact on the fetal cardiovascular system: A review","volume":"2010","author":"Hutter","year":"2010","journal-title":"Int. J. Pediatr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/s41597-019-0253-9","article-title":"Prenatal hypoxia-induced epigenomic and transcriptomic reprogramming in rat fetal and adult offspring hearts","volume":"6","author":"Chen","year":"2019","journal-title":"Sci. Data"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"H1873","DOI":"10.1152\/ajpheart.00870.2020","article-title":"Chronic perinatal hypoxia delays cardiac maturation in a mouse model for cyanotic congenital heart disease","volume":"320","author":"Romanowicz","year":"2021","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1093\/cvr\/cvy277","article-title":"Foetal hypoxia impacts methylome and transcriptome in developmental programming of heart disease","volume":"115","author":"Huang","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Paradis, A.N., Gay, M.S., Wilson, C.G., and Zhang, L. (2015). Newborn hypoxia\/anoxia inhibits cardiomyocyte proliferation and decreases cardiomyocyte endowment in the developing heart: Role of endothelin-1. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116600"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1161\/01.CIR.103.18.2272","article-title":"Influence of hypoxia on nitric oxide synthase activity and gene expression in children with congenital heart disease: A novel pathophysiological adaptive mechanism","volume":"103","author":"Ferreiro","year":"2001","journal-title":"Circulation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1161\/HYPERTENSIONAHA.118.11363","article-title":"Maternal Allopurinol Prevents Cardiac Dysfunction in Adult Male Offspring Programmed by Chronic Hypoxia During Pregnancy","volume":"72","author":"Niu","year":"2018","journal-title":"Hypertension"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"L1444","DOI":"10.1152\/ajplung.00175.2007","article-title":"Nitric oxide and superoxide generation from endothelial NOS: Modulation by HSP90","volume":"293","author":"Sud","year":"2007","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"22268","DOI":"10.1074\/jbc.M001644200","article-title":"Reconstitution of an endothelial nitric-oxide synthase (eNOS), hsp90, and caveolin-1 complex in vitro. Evidence that hsp90 facilitates calmodulin stimulated displacement of eNOS from caveolin-1","volume":"275","author":"Gratton","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hula, N., Liu, R., Spaans, F., Pasha, M., Quon, A., Kirschenman, R., Cooke, C.M., and Davidge, S.T. (2022). The Long-Term Effects of Prenatal Hypoxia on Coronary Artery Function of the Male and Female Offspring. Biomedicines, 10.","DOI":"10.3390\/biomedicines10123019"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3679","DOI":"10.1021\/bi500076r","article-title":"Hypoxia and reoxygenation induce endothelial nitric oxide synthase uncoupling in endothelial cells through tetrahydrobiopterin depletion and S-glutathionylation","volume":"53","author":"Hemann","year":"2014","journal-title":"Biochemistry"},{"key":"ref_33","first-page":"3547","article-title":"PI3K\/Akt and HIF-1 signaling pathway in hypoxia-ischemia (Review)","volume":"18","author":"Zhang","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1161\/01.RES.86.3.319","article-title":"Hypoxic regulation of inducible nitric oxide synthase via hypoxia inducible factor-1 in cardiac myocytes","volume":"86","author":"Jung","year":"2000","journal-title":"Circ. Res."},{"key":"ref_35","first-page":"169","article-title":"Neurochemical Status of Nitric Oxide in the Settings of the Norm, Ishemic Event of Central Nervous System, and Pharmacological Bn Intervention","volume":"315","author":"Belenichev","year":"2021","journal-title":"Georgian Med. News"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12979-015-0046-8","article-title":"Heat shock proteins and hormesis in the diagnosis and treatment of neurodegenerative diseases","volume":"12","author":"Dattilo","year":"2015","journal-title":"Immun. Ageing"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1131683","DOI":"10.3389\/fncel.2023.1131683","article-title":"Involvement of heat shock proteins HSP70 in the mechanisms of endogenous neuroprotection: The prospect of using HSP70 modulators","volume":"17","author":"Belenichev","year":"2023","journal-title":"Front. Cell Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/S0962-8924(00)01900-0","article-title":"Nitric oxide and the regulation of gene expression","volume":"11","author":"Bogdan","year":"2001","journal-title":"Trends Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1515\/BC.2003.153","article-title":"Nitrosative stress and transcription","volume":"384","author":"Kroncke","year":"2003","journal-title":"Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.freeradbiomed.2019.10.411","article-title":"iNOS as a metabolic enzyme under stress conditions","volume":"146","author":"Anavi","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/j.placenta.2015.08.012","article-title":"L-arginine prevents hypoxia-induced vasoconstriction in dual-perfused human placental cotyledons","volume":"36","author":"Bednov","year":"2015","journal-title":"Placenta"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Popazova, O., Belenichev, I., Bukhtiyarova, N., Ryzhenko, V., Oksenych, V., and Kamyshnyi, A. (2023). Cardioprotective Activity of Pharmacological Agents Affecting NO Production and Bioavailability in the Early Postnatal Period after Intrauterine Hypoxia in Rats. Biomedicines, 11.","DOI":"10.3390\/biomedicines11102854"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/S0022-2828(03)00084-1","article-title":"H(2)O(2) regulates cardiac myocyte phenotype via concentration-dependent activation of distinct kinase pathways","volume":"35","author":"Kwon","year":"2003","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1006\/jmcc.2000.1285","article-title":"Reactive oxygen species mediate alpha-adrenergic receptor-stimulated hypertrophy in adult rat ventricular myocytes","volume":"33","author":"Amin","year":"2001","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1161\/hc0402.102863","article-title":"Involvement of nuclear factor-kappaB and apoptosis signal-regulating kinase 1 in G-protein-coupled receptor agonist-induced cardiomyocyte hypertrophy","volume":"105","author":"Hirotani","year":"2002","journal-title":"Circulation"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.1161\/CIR.0000000000000682","article-title":"Cardiomyopathy in Children: Classification and Diagnosis: A Scientific Statement From the American Heart Association","volume":"140","author":"Lipshultz","year":"2019","journal-title":"Circulation"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kumar, S., Kumar, V., and Kim, J.J. (2020). Sarcomeric Gene Variants and Their Role with Left Ventricular Dysfunction in Background of Coronary Artery Disease. Biomolecules, 10.","DOI":"10.3390\/biom10030442"},{"key":"ref_48","first-page":"69","article-title":"Familial hypertrophic cardiomyopathy: Genes, mutations and animal models. A review","volume":"45","author":"Ramirez","year":"2004","journal-title":"Investig. Clin."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5515","DOI":"10.1038\/ncomms6515","article-title":"Mybpc3 gene therapy for neonatal cardiomyopathy enables long-term disease prevention in mice","volume":"5","author":"Mearini","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1126\/science.1236921","article-title":"Allele-specific silencing of mutant Myh6 transcripts in mice suppresses hypertrophic cardiomyopathy","volume":"342","author":"Jiang","year":"2013","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"632293","DOI":"10.3389\/fped.2021.632293","article-title":"Hypertrophic Cardiomyopathy in Children: Pathophysiology, Diagnosis, and Treatment of Non-sarcomeric Causes","volume":"9","author":"Monda","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1038\/ng2073","article-title":"Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy","volume":"39","author":"Pandit","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.hfc.2017.12.005","article-title":"Clinical Presentation and Natural History of Hypertrophic Cardiomyopathy in RASopathies","volume":"14","author":"Calcagni","year":"2018","journal-title":"Heart Fail. Clin."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1172\/JCI44929","article-title":"MEK-ERK pathway modulation ameliorates disease phenotypes in a mouse model of Noonan syndrome associated with the Raf1(L613V) mutation","volume":"121","author":"Wu","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1172\/JCI44972","article-title":"Rapamycin reverses hypertrophic cardiomyopathy in a mouse model of LEOPARD syndrome-associated PTPN11 mutation","volume":"121","author":"Marin","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1002\/ajmg.a.36982","article-title":"Rapidly progressive hypertrophic cardiomyopathy in an infant with Noonan syndrome with multiple lentigines: Palliative treatment with a rapamycin analog","volume":"167A","author":"Hahn","year":"2015","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Zhang, J., Cao, L., Tan, Y., Zheng, Y., and Gui, Y. (2021). N-acetylcysteine protects neonatal mice from ventricular hypertrophy induced by maternal obesity in a sex-specific manner. Biomed. Pharmacother., 133.","DOI":"10.1016\/j.biopha.2020.110989"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s000180300001","article-title":"Molecular mechanisms of N-acetylcysteine actions","volume":"60","author":"Zafarullah","year":"2003","journal-title":"Cell Mol. Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1146\/annurev-genom-091416-035426","article-title":"Recent Advances in Mitochondrial Disease","volume":"18","author":"Craven","year":"2017","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1016\/j.cjca.2015.08.017","article-title":"Mitochondrial Diseases and Cardiomyopathies","volume":"31","author":"Levtova","year":"2015","journal-title":"Can. J. Cardiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1016\/j.bbagen.2013.12.025","article-title":"Mitochondrial respiratory chain disorders in childhood: Insights into diagnosis and management in the new era of genomic medicine","volume":"1840","author":"Menezes","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Yang, J., Chen, S., Duan, F., Wang, X., Zhang, X., Lian, B., Kou, M., Chiang, Z., Li, Z., and Lian, Q. (2022). Mitochondrial Cardiomyopathy: Molecular Epidemiology, Diagnosis, Models, and Therapeutic Management. Cells, 11.","DOI":"10.3390\/cells11213511"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1097\/FJC.0000000000000599","article-title":"Cardioprotective Effects of Metformin","volume":"72","author":"Driver","year":"2018","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Dziubak, A., Wojcicka, G., Wojtak, A., and Beltowski, J. (2018). Metabolic Effects of Metformin in the Failing Heart. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19102869"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e13096","DOI":"10.1111\/acel.13096","article-title":"Metformin mediates cardioprotection against aging-induced ischemic necroptosis","volume":"19","author":"Li","year":"2020","journal-title":"Aging Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/s41419-022-05075-2","article-title":"RNA-based therapeutics: An overview and prospectus","volume":"13","author":"Zhu","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1007\/s40265-022-01728-w","article-title":"Pharmacological Management of Hypertrophic Cardiomyopathy: From Bench to Bedside","volume":"82","author":"Palandri","year":"2022","journal-title":"Drugs"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/4\/477\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:27:43Z","timestamp":1760106463000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/4\/477"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,13]]},"references-count":67,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["biom14040477"],"URL":"https:\/\/doi.org\/10.3390\/biom14040477","relation":{},"ISSN":["2218-273X"],"issn-type":[{"type":"electronic","value":"2218-273X"}],"subject":[],"published":{"date-parts":[[2024,4,13]]}}}