{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:09:12Z","timestamp":1792804152952,"version":"4.5.0"},"reference-count":83,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T00:00:00Z","timestamp":1664755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council of Australia","doi-asserted-by":"publisher","award":["APP1062120"],"award-info":[{"award-number":["APP1062120"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council of Australia","doi-asserted-by":"publisher","award":["APP1059960"],"award-info":[{"award-number":["APP1059960"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council of Australia","doi-asserted-by":"publisher","award":["APP1078985"],"award-info":[{"award-number":["APP1078985"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Alice Baker and Eleanor Shaw Fellowship (The Baker Foundation, Australia)","award":["APP1062120"],"award-info":[{"award-number":["APP1062120"]}]},{"name":"Alice Baker and Eleanor Shaw Fellowship (The Baker Foundation, Australia)","award":["APP1059960"],"award-info":[{"award-number":["APP1059960"]}]},{"name":"Alice Baker and Eleanor Shaw Fellowship (The Baker Foundation, Australia)","award":["APP1078985"],"award-info":[{"award-number":["APP1078985"]}]},{"DOI":"10.13039\/501100000925","name":"Fellowships from the National Health and Medical Research Council of Australia","doi-asserted-by":"publisher","award":["APP1062120"],"award-info":[{"award-number":["APP1062120"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Fellowships from the National Health and Medical Research Council of Australia","doi-asserted-by":"publisher","award":["APP1059960"],"award-info":[{"award-number":["APP1059960"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Fellowships from the National Health and Medical Research Council of Australia","doi-asserted-by":"publisher","award":["APP1078985"],"award-info":[{"award-number":["APP1078985"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Victorian Government\u2019s Operational Infrastructure Support Program","award":["APP1062120"],"award-info":[{"award-number":["APP1062120"]}],"id":[{"id":"https:\/\/ror.org\/02xvc5r05","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Victorian Government\u2019s Operational Infrastructure Support Program","award":["APP1059960"],"award-info":[{"award-number":["APP1059960"]}],"id":[{"id":"https:\/\/ror.org\/02xvc5r05","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Victorian Government\u2019s Operational Infrastructure Support Program","award":["APP1078985"],"award-info":[{"award-number":["APP1078985"]}],"id":[{"id":"https:\/\/ror.org\/02xvc5r05","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>MicroRNA 34a (miR-34a) is elevated in the heart in a setting of cardiac stress or pathology, and we previously reported that inhibition of miR-34a in vivo provided protection in a setting of pressure overload-induced pathological cardiac hypertrophy and dilated cardiomyopathy. Prior work had also shown that circulating or cardiac miR-34a was elevated in a setting of diabetes. However, the therapeutic potential of inhibiting miR-34a in vivo in the diabetic heart had not been assessed. In the current study, type 1 diabetes was induced in adult male mice with 5 daily injections of streptozotocin (STZ). At 8 weeks post-STZ, when mice had established type 1 diabetes and diastolic dysfunction, mice were administered locked nucleic acid (LNA)-antimiR-34a or saline-control with an eight-week follow-up. Cardiac function, cardiac morphology, cardiac fibrosis, capillary density and gene expression were assessed. Diabetic mice presented with high blood glucose, elevated liver and kidney weights, diastolic dysfunction, mild cardiac enlargement, cardiac fibrosis and reduced myocardial capillary density. miR-34a was elevated in the heart of diabetic mice in comparison to non-diabetic mice. Inhibition of miR-34a had no significant effect on diastolic function or atrial enlargement, but had a mild effect on preventing an elevation in cardiac enlargement, fibrosis and ventricular gene expression of B-type natriuretic peptide (BNP) and the anti-angiogenic miRNA (miR-92a). A miR-34a target, vinculin, was inversely correlated with miR-34a expression, but other miR-34a targets were unchanged. In summary, inhibition of miR-34a provided limited protection in a mouse model with established type 1 diabetes-induced cardiomyopathy and failed to improve diastolic function. Given diabetes represents a systemic disorder with numerous miRNAs dysregulated in the diabetic heart, as well as other organs, strategies targeting multiple miRNAs and\/or earlier intervention is likely to be required.<\/jats:p>","DOI":"10.3390\/cells11193117","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T01:52:21Z","timestamp":1665193941000},"page":"3117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["In Vivo Inhibition of miR-34a Modestly Limits Cardiac Enlargement and Fibrosis in a Mouse Model with Established Type 1 Diabetes-Induced Cardiomyopathy, but Does Not Improve Diastolic Function"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4534-0549","authenticated-orcid":false,"given":"Bianca C.","family":"Bernardo","sequence":"first","affiliation":[{"name":"Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia"},{"name":"Department of Diabetes, Central Clinical School, Monash University, Clayton, VIC 3800, Australia"},{"name":"Department of Paediatrics, University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunes S.","family":"Yildiz","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Kiriazis","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia"},{"name":"Baker Department of Cardiometabolic Health, University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia A.","family":"Harmawan","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celeste M. K.","family":"Tai","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8610-0058","authenticated-orcid":false,"given":"Rebecca H.","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia"},{"name":"Monash Institute of Pharmaceutical Sciences, Monash University, Royal Parade, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8316-1066","authenticated-orcid":false,"given":"Julie R.","family":"McMullen","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia"},{"name":"Department of Diabetes, Central Clinical School, Monash University, Clayton, VIC 3800, Australia"},{"name":"Baker Department of Cardiometabolic Health, University of Melbourne, Parkville, VIC 3010, Australia"},{"name":"Department of Physiology, Monash University, Clayton, VIC 3800, Australia"},{"name":"Department of Physiology, Anatomy and Microbiology, La Trobe University, Melbourne, VIC 3086, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.diabres.2018.02.023","article-title":"IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045","volume":"138","author":"Cho","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1161\/01.CIR.101.19.2271","article-title":"Impact of diabetes on cardiac structure and function: The strong heart study","volume":"101","author":"Devereux","year":"2000","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3213","DOI":"10.1161\/CIRCULATIONAHA.106.679597","article-title":"Diabetic Cardiomyopathy Revisited","volume":"115","author":"Boudina","year":"2007","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1001\/jama.298.7.765","article-title":"Diabetes and mortality following acute coronary syndromes","volume":"298","author":"Donahoe","year":"2007","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1161\/CIRCRESAHA.120.315913","article-title":"Basic Mechanisms of Diabetic Heart Disease","volume":"126","author":"Ritchie","year":"2020","journal-title":"Circ. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.pharmthera.2014.01.003","article-title":"Diabetic cardiomyopathy: Mechanisms and new treatment strategies targeting antioxidant signaling pathways","volume":"142","author":"Huynh","year":"2014","journal-title":"Pharmacol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.jacc.2017.11.019","article-title":"Implications of Underlying Mechanisms for the Recognition and Management of Diabetic Cardiomyopathy","volume":"71","author":"Marwick","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1161\/CIRCULATIONAHA.107.704080","article-title":"New drugs for the treatment of diabetes mellitus: Part I: Thiazolidinediones and their evolving cardiovascular implications","volume":"117","author":"McGuire","year":"2008","journal-title":"Circulation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"428","DOI":"10.2337\/dc09-1499","article-title":"Incretin-based therapies for the treatment of type 2 diabetes: Evaluation of the risks and benefits","volume":"33","author":"Drucker","year":"2010","journal-title":"Diabetes Care."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.hlc.2011.11.002","article-title":"A MicroRNA Guide for Clinicians and Basic Scientists: Background and Experimental Techniques","volume":"21","author":"Bernardo","year":"2012","journal-title":"Heart Lung Circ."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1007\/s00204-020-02709-2","article-title":"Clusterin is regulated by IGF1-PI3K signaling in the heart: Implications for biomarker and drug target discovery, and cardiotoxicity","volume":"94","author":"Ooi","year":"2020","journal-title":"Arch. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.4155\/fmc.15.107","article-title":"miRNA therapeutics: A new class of drugs with potential therapeutic applications in the heart","volume":"7","author":"Bernardo","year":"2015","journal-title":"Future Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1056\/NEJMoa1209026","article-title":"Treatment of HCV infection by targeting microRNA","volume":"368","author":"Janssen","year":"2013","journal-title":"New Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jare.2020.08.012","article-title":"Therapeutic advances of miRNAs: A preclinical and clinical update","volume":"28","author":"Chakraborty","year":"2021","journal-title":"J. Adv. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nrd.2016.246","article-title":"MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases","volume":"16","author":"Rupaimoole","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_16","first-page":"633","article-title":"Differentially expressed microRNAs and their target genes in the hearts of streptozotocin-induced diabetic mice","volume":"4","author":"Diao","year":"2011","journal-title":"Mol. Med. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/dmrr.1054","article-title":"miR133a regulates cardiomyocyte hypertrophy in diabetes","volume":"26","author":"Feng","year":"2010","journal-title":"Diabetes Metab Res. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Bernardo, B.C., Gao, X.M., Tham, Y.K., Kiriazis, H., Winbanks, C.E., Ooi, J.Y., Boey, E.J., Obad, S., Kauppinen, S., and Gregorevic, P. (2014). Silencing of miR-34a attenuates cardiac dysfunction in a setting of moderate, but not severe, hypertrophic cardiomyopathy. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090337"},{"key":"ref_19","first-page":"1355","article-title":"MicroRNA-34a regulates cardiac fibrosis after myocardial infarction by targeting Smad4","volume":"18","author":"Huang","year":"2014","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1161\/CIRCRESAHA.117.305962","article-title":"MicroRNA-34a Plays a Key Role in Cardiac Repair and Regeneration Following Myocardial Infarction","volume":"117","author":"Yang","year":"2015","journal-title":"Circ. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5959","DOI":"10.1113\/JP272512","article-title":"Sex differences in response to miRNA-34a therapy in mouse models of cardiac disease: Identification of sex-, disease- and treatment-regulated miRNAs","volume":"594","author":"Bernardo","year":"2016","journal-title":"J. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17615","DOI":"10.1073\/pnas.1206432109","article-title":"Therapeutic inhibition of the miR-34 family attenuates pathological cardiac remodeling and improves heart function","volume":"109","author":"Bernardo","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nature11919","article-title":"MicroRNA-34a regulates cardiac ageing and function","volume":"495","author":"Boon","year":"2013","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1161\/CIRCULATIONAHA.107.687947","article-title":"MicroRNAs in the Human Heart: A Clue to Fetal Gene Reprogramming in Heart Failure","volume":"116","author":"Thum","year":"2007","journal-title":"Circulation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1042\/CS20110563","article-title":"MicroRNA-34a regulates the longevity-associated protein SIRT1 in coronary artery disease: Effect of statins on SIRT1 and microRNA-34a expression","volume":"123","author":"Tabuchi","year":"2012","journal-title":"Clin. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s00592-010-0226-0","article-title":"Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: A clinical study","volume":"48","author":"Kong","year":"2011","journal-title":"Acta Diabetol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1038\/s41418-017-0047-6","article-title":"Diabetes induces the activation of pro-ageing miR-34a in the heart, but has differential effects on cardiomyocytes and cardiac progenitor cells","volume":"25","author":"Saw","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1042\/CS20170063","article-title":"Phosphoinositide 3-kinase (p110alpha) gene delivery limits diabetes-induced cardiac NADPH oxidase and cardiomyopathy in a mouse model with established diastolic dysfunction","volume":"131","author":"Prakoso","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1093\/cvr\/cvab043","article-title":"Fine-tuning the cardiac O-GlcNAcylation regulatory enzymes governs the functional and structural phenotype of the diabetic heart","volume":"118","author":"Prakoso","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3389\/fphys.2020.00124","article-title":"Defining the Progression of Diabetic Cardiomyopathy in a Mouse Model of Type 1 Diabetes","volume":"11","author":"Huynh","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"22442","DOI":"10.1038\/srep22442","article-title":"Inhibition of miR-154 Protects Against Cardiac Dysfunction and Fibrosis in a Mouse Model of Pressure Overload","volume":"6","author":"Bernardo","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5097","DOI":"10.1096\/fj.14-253856","article-title":"Therapeutic silencing of miR-652 restores heart function and attenuates adverse remodeling in a setting of established pathological hypertrophy","volume":"28","author":"Bernardo","year":"2014","journal-title":"FASEB J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/ng.786","article-title":"Silencing of microRNA families by seed-targeting tiny LNAs","volume":"43","author":"Obad","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"H627","DOI":"10.1152\/ajpheart.00327.2019","article-title":"CORP: Practical tools for improving experimental design and reporting of laboratory studies of cardiovascular physiology and metabolism","volume":"317","author":"Weeks","year":"2019","journal-title":"Am. J. Physiol. -Heart Circ. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"H58","DOI":"10.1152\/ajpheart.00157.2018","article-title":"Improving the quality of preclinical research echocardiography: Observations, training, and guidelines for measurement","volume":"315","author":"Donner","year":"2018","journal-title":"Am. J. Physiol Heart Circ. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"A251","DOI":"10.1161\/atvb.38.suppl_1.251","article-title":"Abstract 251: miRNA Mapping of Cardiac Endothelial and Fibroblast Cells during Hypertrophy Progression","volume":"38","author":"Dangwal","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.freeradbiomed.2013.02.021","article-title":"Targeting the Upregulation of Reactive Oxygen Species Subsequent to Hyperglycemia Prevents Type 1 Diabetic Cardiomyopathy in Mice","volume":"60","author":"Huynh","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.2337\/db09-1456","article-title":"Cardiac-specific IGF-1 receptor transgenic expression protects against cardiac fibrosis and diastolic dysfunction in a mouse model of diabetic cardiomyopathy","volume":"59","author":"Huynh","year":"2010","journal-title":"Diabetes"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1007\/s00125-012-2720-0","article-title":"Enhanced phosphoinositide 3-kinase(p110alpha) activity prevents diabetes-induced cardiomyopathy and superoxide generation in a mouse model of diabetes","volume":"55","author":"Ritchie","year":"2012","journal-title":"Diabetologia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1172\/JCI24682","article-title":"Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure","volume":"115","author":"Shiojima","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Nalls, D., Tang, S.N., Rodova, M., Srivastava, R.K., and Shankar, S. (2011). Targeting epigenetic regulation of miR-34a for treatment of pancreatic cancer by inhibition of pancreatic cancer stem cells. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024099"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ye, W., Lv, Q., Wong, C.K., Hu, S., Fu, C., Hua, Z., Cai, G., Li, G., Yang, B.B., and Zhang, Y. (2008). The effect of central loops in miRNA:MRE duplexes on the efficiency of miRNA-mediated gene regulation. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001719"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7522","DOI":"10.1128\/MCB.00728-07","article-title":"Cardiac-myocyte-specific excision of the vinculin gene disrupts cellular junctions, causing sudden death or dilated cardiomyopathy","volume":"27","author":"Miller","year":"2007","journal-title":"Mol. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.phrs.2013.06.005","article-title":"MicroRNAs as pharmacological targets in diabetes","volume":"75","author":"Mao","year":"2013","journal-title":"Pharmacol. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1161\/ATVBAHA.109.201988","article-title":"PI3K(p110 alpha) protects against myocardial infarction-induced heart failure: Identification of PI3K-regulated miRNA and mRNA","volume":"30","author":"Lin","year":"2010","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/978-3-319-74470-4_4","article-title":"Targeting miRNA for Therapy of Juvenile and Adult Diabetic Cardiomyopathy","volume":"1056","author":"Nandi","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1016\/j.bbadis.2017.03.013","article-title":"Role of microRNA in diabetic cardiomyopathy: From mechanism to intervention","volume":"1863","author":"Guo","year":"2017","journal-title":"Biochim. Biophys. Acta. Mol. Basis. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1042\/CS20160916","article-title":"Down-regulation of miR-15a\/b accelerates fibrotic remodelling in the Type 2 diabetic human and mouse heart","volume":"131","author":"Rawal","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1093\/eurheartj\/ehv599","article-title":"MicroRNA profiling unveils hyperglycaemic memory in the diabetic heart","volume":"37","author":"Costantino","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1007\/s00125-015-3622-8","article-title":"Silencing of miR-195 reduces diabetic cardiomyopathy in C57BL\/6 mice","volume":"58","author":"Zheng","year":"2015","journal-title":"Diabetologia"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"223","DOI":"10.18632\/aging.100276","article-title":"Gain of survival signaling by down-regulation of three key miRNAs in brain of calorie-restricted mice","volume":"3","author":"Khanna","year":"2011","journal-title":"Aging"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.bbrc.2016.06.051","article-title":"miR-483-3p regulates hyperglycaemia-induced cardiomyocyte apoptosis in transgenic mice","volume":"477","author":"Qiao","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"BSR20201573","DOI":"10.1042\/BSR20201573","article-title":"miRNA-1183-targeted regulation of Bcl-2 contributes to the pathogenesis of rheumatic heart disease","volume":"40","author":"Li","year":"2020","journal-title":"Biosci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2084","DOI":"10.1111\/jcmm.12563","article-title":"MicroRNA-181c targets Bcl-2 and regulates mitochondrial morphology in myocardial cells","volume":"19","author":"Wang","year":"2015","journal-title":"J. Cell Mol. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s00204-012-0965-5","article-title":"MicroRNA-210 targets antiapoptotic Bcl-2 expression and mediates hypoxia-induced apoptosis of neuroblastoma cells","volume":"87","author":"Chio","year":"2013","journal-title":"Arch. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.brainres.2010.08.074","article-title":"MiRNA-451 plays a role as tumor suppressor in human glioma cells","volume":"1359","author":"Nan","year":"2010","journal-title":"Brain Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3389\/fphys.2012.00068","article-title":"MicroRNA Regulation of SIRT1","volume":"3","author":"Yamakuchi","year":"2012","journal-title":"Front. Physiol"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1080\/10715762.2020.1863393","article-title":"MicroRNA-499-5p targets SIRT1 to aggravate lipopolysaccharide-induced acute lung injury","volume":"55","author":"Yang","year":"2021","journal-title":"Free. Radic. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1080\/15476286.2016.1181251","article-title":"Identification of miR-34 regulatory networks in settings of disease and antimiR-therapy: Implications for treating cardiac pathology and other diseases","volume":"14","author":"Ooi","year":"2017","journal-title":"RNA Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1007\/s12035-015-9106-5","article-title":"Serum MicroRNA Signatures in Migraineurs During Attacks and in Pain-Free Periods","volume":"53","author":"Andersen","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Salvoza, N.C., Klinzing, D.C., Gopez-Cervantes, J., and Baclig, M.O. (2016). Association of Circulating Serum miR-34a and miR-122 with Dyslipidemia among Patients with Non-Alcoholic Fatty Liver Disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153497"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cellsig.2018.03.005","article-title":"MiR-34a\/miR-93 target c-Ski to modulate the proliferaton of rat cardiac fibroblasts and extracellular matrix deposition in vivo and in vitro","volume":"46","author":"Zhang","year":"2018","journal-title":"Cell Signal."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/jcmm.12218","article-title":"Cardiac miR-133a overexpression prevents early cardiac fibrosis in diabetes","volume":"18","author":"Chen","year":"2014","journal-title":"J. Cell Mol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"768","DOI":"10.2337\/db15-1033","article-title":"miR-200b Mediates Endothelial-to-Mesenchymal Transition in Diabetic Cardiomyopathy","volume":"65","author":"Feng","year":"2016","journal-title":"Diabetes"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1128\/MCB.01114-15","article-title":"Novel MicroRNA Regulators of Atrial Natriuretic Peptide Production","volume":"36","author":"Wu","year":"2016","journal-title":"Mol. Cell Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1161\/ATVBAHA.118.311298","article-title":"miR-34a Promotes Vascular Smooth Muscle Cell Calcification by Downregulating SIRT1 (Sirtuin 1) and Axl (AXL Receptor Tyrosine Kinase)","volume":"38","author":"Badi","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1126\/science.1174381","article-title":"MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice","volume":"324","author":"Bonauer","year":"2009","journal-title":"Science"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4568","DOI":"10.1111\/jcmm.13700","article-title":"The regulatory role of microRNAs in angiogenesis-related diseases","volume":"22","author":"Sun","year":"2018","journal-title":"J. Cell Mol. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/1755-5922.12113","article-title":"miR-30c Mediates Upregulation of Cdc42 and Pak1 in Diabetic Cardiomyopathy","volume":"33","author":"Raut","year":"2015","journal-title":"Cardiovasc. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3075","DOI":"10.2337\/db16-0023","article-title":"Lack of miR-133a Decreases Contractility of Diabetic Hearts: A Role for Novel Cross Talk Between Tyrosine Aminotransferase and Tyrosine Hydroxylase","volume":"65","author":"Nandi","year":"2016","journal-title":"Diabetes"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3389\/fcvm.2019.00045","article-title":"Transgenic Expression of miR-133a in the Diabetic Akita Heart Prevents Cardiac Remodeling and Cardiomyopathy","volume":"6","author":"Kambis","year":"2019","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"68","DOI":"10.4103\/2229-3485.179431","article-title":"MicroRNA therapeutics: Discovering novel targets and developing specific therapy","volume":"7","author":"Christopher","year":"2016","journal-title":"Perspect Clin. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.3389\/fphar.2018.01090","article-title":"Generation of MicroRNA-34 Sponges and Tough Decoys for the Heart: Developments and Challenges","volume":"9","author":"Bernardo","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/nrd4140","article-title":"MicroRNAs and other non-coding RNAs as targets for anticancer drug development","volume":"12","author":"Ling","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/s41569-019-0218-x","article-title":"RNA-based diagnostic and therapeutic strategies for cardiovascular disease","volume":"16","author":"Lu","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Laggerbauer, B., and Engelhardt, S. (2022). MicroRNAs as therapeutic targets in cardiovascular disease. J. Clin. Investig., 132.","DOI":"10.1172\/JCI159179"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.omtn.2022.07.007","article-title":"Therapeutic knockdown of miR-320 improves deteriorated cardiac function in a pre-clinical model of non-ischemic diabetic heart disease","volume":"29","author":"Ghosh","year":"2022","journal-title":"Mol. Therapy. Nucleic Acids"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.1182\/blood-2018-99-119861","article-title":"Phase 1 Trial of Cobomarsen, an Inhibitor of Mir-155, in Cutaneous T Cell Lymphoma","volume":"132","author":"Querfeld","year":"2018","journal-title":"Blood"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1089\/nat.2020.0871","article-title":"Efficiency and Target Derepression of Anti-miR-92a: Results of a First in Human Study","volume":"30","author":"Abplanalp","year":"2020","journal-title":"Nucleic. Acid. Ther."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Silva, J., and da Costa Martins, P.A. (2022). Non-Coding RNAs in the Therapeutic Landscape of Pathological Cardiac Hypertrophy. Cells, 11.","DOI":"10.3390\/cells11111805"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/s41573-021-00219-z","article-title":"Noncoding RNA therapeutics\u2014Challenges and potential solutions","volume":"20","author":"Winkle","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"7088","DOI":"10.7150\/thno.34895","article-title":"Ultrasound and Microbubble-targeted Delivery of a microRNA Inhibitor to the Heart Suppresses Cardiac Hypertrophy and Preserves Cardiac Function","volume":"9","author":"Kopechek","year":"2019","journal-title":"Theranostics"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e3100","DOI":"10.1038\/cddis.2017.495","article-title":"Alternative mechanisms of miR-34a regulation in cancer","volume":"8","author":"Culig","year":"2017","journal-title":"Cell Death Dis."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/19\/3117\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:46:07Z","timestamp":1760143567000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/19\/3117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,3]]},"references-count":83,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["cells11193117"],"URL":"https:\/\/doi.org\/10.3390\/cells11193117","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,3]]}}}