{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:28:30Z","timestamp":1792639710725,"version":"4.5.0"},"reference-count":62,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T00:00:00Z","timestamp":1672963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Universities and Research","award":["2017NKB2N4_005"],"award-info":[{"award-number":["2017NKB2N4_005"]}]},{"name":"Ministry of Education, Universities and Research","award":["20203YAYGB_005"],"award-info":[{"award-number":["20203YAYGB_005"]}]},{"name":"Ministry of Education, Universities and Research","award":["2020L45ZWA_005"],"award-info":[{"award-number":["2020L45ZWA_005"]}]},{"name":"Ministry of Education, Universities and Research","award":["PON-AIM \u2013 1829805-2"],"award-info":[{"award-number":["PON-AIM \u2013 1829805-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The main cause of morbidity and mortality in diabetes mellitus (DM) is cardiovascular complications. Diabetic cardiomyopathy (DCM) remains incompletely understood. Animal models have been crucial in exploring DCM pathophysiology while identifying potential therapeutic targets. Streptozotocin (STZ) has been widely used to produce experimental models of both type 1 and type 2 DM (T1DM and T2DM). Here, we compared these two models for their effects on cardiac structure, function and transcriptome. Different doses of STZ and diet chows were used to generate T1DM and T2DM in C57BL\/6J mice. Normal euglycemic and nonobese sex- and age-matched mice served as controls (CTRL). Immunohistochemistry, RT-PCR and RNA-seq were employed to compare hearts from the three animal groups. STZ-induced T1DM and T2DM affected left ventricular function and myocardial performance differently. T1DM displayed exaggerated apoptotic cardiomyocyte (CM) death and reactive hypertrophy and fibrosis, along with increased cardiac oxidative stress, CM DNA damage and senescence, when compared to T2DM in mice. T1DM and T2DM affected the whole cardiac transcriptome differently. In conclusion, the STZ-induced T1DM and T2DM mouse models showed significant differences in cardiac remodeling, function and the whole transcriptome. These differences could be of key relevance when choosing an animal model to study specific features of DCM.<\/jats:p>","DOI":"10.3390\/ijms24021132","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T01:36:17Z","timestamp":1673228177000},"page":"1132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["Streptozotocin-Induced Type 1 and 2 Diabetes Mellitus Mouse Models Show Different Functional, Cellular and Molecular Patterns of Diabetic Cardiomyopathy"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9043-6032","authenticated-orcid":false,"given":"Fabiola","family":"Marino","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Salerno","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Scalise","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Salerno","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2479-6018","authenticated-orcid":false,"given":"Annalaura","family":"Torella","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Molinaro","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Chiefalo","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Filardo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Siracusa","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Panuccio","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0758-5059","authenticated-orcid":false,"given":"Carlo","family":"Ferravante","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u2018Scuola Medica Salernitana\u2032, University of Salerno, 84081 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0538-8978","authenticated-orcid":false,"given":"Giorgio","family":"Giurato","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u2018Scuola Medica Salernitana\u2032, University of Salerno, 84081 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1783-5015","authenticated-orcid":false,"given":"Francesca","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u2018Scuola Medica Salernitana\u2032, University of Salerno, 84081 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Torella","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science, University of Campania \u201cL. Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Donniacuo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cL. Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"De Angelis","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cL. Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Viglietto","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Urbanek","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, Federico II University, 88121 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0455-2083","authenticated-orcid":false,"given":"Alessandro","family":"Weisz","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u2018Scuola Medica Salernitana\u2032, University of Salerno, 84081 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4915-5084","authenticated-orcid":false,"given":"Daniele","family":"Torella","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1675-2093","authenticated-orcid":false,"given":"Eleonora","family":"Cianflone","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,6]]},"reference":[{"key":"ref_1","unstructured":"NCD Risk Factor Collaboration (2016). Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants. Lancet, 387, 1513\u20131530."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.diabres.2011.10.040","article-title":"The International Diabetes Federation diabetes atlas methodology for estimating global and national prevalence of diabetes in adults","volume":"94","author":"Guariguata","year":"2011","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"383","DOI":"10.4239\/wjd.v12.i4.383","article-title":"Diabetic heart disease: A clinical update","volume":"12","author":"Rajbhandari","year":"2021","journal-title":"World J. Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e011295","DOI":"10.1161\/JAHA.118.011295","article-title":"Diabetes Mellitus-Related All-Cause and Cardiovascular Mortality in a National Cohort of Adults","volume":"8","author":"Raghavan","year":"2019","journal-title":"J. Am. Heart Assoc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.4239\/wjd.v6.i13.1246","article-title":"Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research","volume":"6","author":"Leon","year":"2015","journal-title":"World J. Diabetes"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"52","DOI":"10.15420\/cfr.2016:20:2","article-title":"Heart Failure in Patients with Diabetes Mellitus","volume":"3","author":"Rosano","year":"2017","journal-title":"Card. Fail. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-Perez, A.M., Damas-Fuentes, M., Cornejo-Pareja, I., and Tinahones, F.J. (2021). Heart Failure in Type 1 Diabetes: A Complication of Concern? A Narrative Review. J. Clin. Med., 10.","DOI":"10.3390\/jcm10194497"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Palazzuoli, A., and Iacoviello, M. (2022). Diabetes leading to heart failure and heart failure leading to diabetes: Epidemiological and clinical evidence. Heart Fail. Rev.","DOI":"10.1007\/s10741-022-10238-6"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.2337\/dci22-0032","article-title":"Microvascular Disease and the Pathogenesis of Heart Failure in Diabetes: A Tiny Piece of the Tricky Puzzle","volume":"45","author":"Trimarco","year":"2022","journal-title":"Diabetes Care"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.2337\/dc20-2173","article-title":"Contemporary Management of Heart Failure in Patients With Diabetes","volume":"43","author":"Shaw","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1161\/CIRCRESAHA.117.311586","article-title":"Diabetic Cardiomyopathy: An Update of Mechanisms Contributing to This Clinical Entity","volume":"122","author":"Jia","year":"2018","journal-title":"Circ. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2042018819834869","DOI":"10.1177\/2042018819834869","article-title":"Diabetic cardiomyopathy: Prevalence, determinants and potential treatments","volume":"10","author":"Gulsin","year":"2019","journal-title":"Ther. Adv. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"220","DOI":"10.4103\/jcecho.jcecho_36_21","article-title":"A Subtle Decline in Cardiac Mechanics is correlated with Albuminuria in Asymptomatic Normotensive Patients with Type 2 Diabetes Mellitus: A Two Dimensional Strain Echocardiography Study","volume":"31","author":"Abdellatif","year":"2021","journal-title":"J. Cardiovasc. Echogr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101530","DOI":"10.1016\/j.eclinm.2022.101530","article-title":"Myocardial regeneration protocols towards the routine clinical scenario: An unseemly path from bench to bedside","volume":"50","author":"Salerno","year":"2022","journal-title":"EClinicalMedicine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/0471141755.ph0547s70","article-title":"Streptozotocin-Induced Diabetic Models in Mice and Rats","volume":"70","author":"Furman","year":"2015","journal-title":"Curr. Protoc. Pharmacol."},{"key":"ref_16","first-page":"181","article-title":"Streptozotocin-induced type 1 diabetes in rodents as a model for studying mitochondrial mechanisms of diabetic \u03b2 cell glucotoxicity","volume":"8","author":"Wu","year":"2015","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"719","DOI":"10.4314\/ahs.v21i2.30","article-title":"Streptozotocin-induced type 1 and 2 diabetes in rodents: A model for studying diabetic cardiac autonomic neuropathy","volume":"21","author":"Akinlade","year":"2021","journal-title":"Afr. Health Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1177\/0023677213489548","article-title":"Streptozotocin is equally diabetogenic whether administered to fed or fasted mice","volume":"47","author":"Chaudhry","year":"2013","journal-title":"Lab. Anim."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/2251-6581-12-60","article-title":"Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans","volume":"12","author":"Eleazu","year":"2013","journal-title":"J. Diabetes Metab. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2902351","DOI":"10.1155\/2016\/2902351","article-title":"An Overview of Murine High Fat Diet as a Model for Type 2 Diabetes Mellitus","volume":"2016","author":"Heydemann","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/s41569-020-0339-2","article-title":"Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: Preclinical and clinical evidence","volume":"17","author":"Tan","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.2337\/db21-0536","article-title":"Diabetes-Induced Cellular Senescence and Senescence-Associated Secretory Phenotype Impair Cardiac Regeneration and Function Independently of Age","volume":"71","author":"Marino","year":"2022","journal-title":"Diabetes"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"111740","DOI":"10.1016\/j.mad.2022.111740","article-title":"Pharmacological clearance of senescent cells improves cardiac remodeling and function after myocardial infarction in female aged mice","volume":"208","author":"Salerno","year":"2022","journal-title":"Mech. Ageing Dev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1586\/erc.10.17","article-title":"Diabetic cardiomyopathy: Signaling defects and therapeutic approaches","volume":"8","author":"Dobrin","year":"2010","journal-title":"Expert Rev. Cardiovasc. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.2337\/diabetes.51.6.1938","article-title":"Hyperglycemia-induced apoptosis in mouse myocardium: Mitochondrial cytochrome C-mediated caspase-3 activation pathway","volume":"51","author":"Cai","year":"2002","journal-title":"Diabetes"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1161\/01.RES.87.12.1123","article-title":"Myocardial cell death in human diabetes","volume":"87","author":"Frustaci","year":"2000","journal-title":"Circ. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/s41419-019-1655-5","article-title":"c-kit Haploinsufficiency impairs adult cardiac stem cell growth, myogenicity and myocardial regeneration","volume":"10","author":"Aquila","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Cianflone, E., Cappetta, D., Mancuso, T., Sabatino, J., Marino, F., Scalise, M., Albanese, M., Salatino, A., Parrotta, E.I., and Cuda, G. (2020). Statins Stimulate New Myocyte Formation After Myocardial Infarction by Activating Growth and Differentiation of the Endogenous Cardiac Stem Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21217927"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"869414","DOI":"10.3389\/fendo.2022.869414","article-title":"Cellular Senescence in Diabetes Mellitus: Distinct Senotherapeutic Strategies for Adipose Tissue and Pancreatic \u03b2 Cells","volume":"13","author":"Murakami","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Molinaro, C., Salerno, L., Marino, F., Scalise, M., Salerno, N., Pagano, L., De Angelis, A., Cianflone, E., Torella, D., and Urbanek, K. (2022). Unraveling and Targeting Myocardial Regeneration Deficit in Diabetes. Antioxidants, 11.","DOI":"10.3390\/antiox11020208"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e100492","DOI":"10.15252\/embj.2018100492","article-title":"Length-independent telomere damage drives post-mitotic cardiomyocyte senescence","volume":"38","author":"Anderson","year":"2019","journal-title":"EMBO J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1093\/eurheartj\/ehz486","article-title":"2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD","volume":"41","author":"Cosentino","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s10741-011-9257-z","article-title":"Diabetic cardiomyopathy: Understanding the molecular and cellular basis to progress in diagnosis and treatment","volume":"17","year":"2012","journal-title":"Heart Fail. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"703355","DOI":"10.3389\/fcvm.2021.703355","article-title":"Research(\u2019s) Sweet Hearts: Experimental Biomedical Models of Diabetic Cardiomyopathy","volume":"8","author":"Richter","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s11892-008-0042-x","article-title":"The complexities of diabetic cardiomyopathy: Lessons from patients and animal models","volume":"8","author":"Harmancey","year":"2008","journal-title":"Curr. Diabetes Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s42826-021-00101-4","article-title":"Experimental animal models for diabetes and its related complications-a review","volume":"37","author":"Kottaisamy","year":"2021","journal-title":"Lab. Anim. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"mjac028","DOI":"10.1093\/jmcb\/mjac028","article-title":"Heart failure with preserved ejection fraction (HFpEF) in type 2 diabetes mellitus: From pathophysiology to therapeutics","volume":"14","author":"Abudureyimu","year":"2022","journal-title":"J. Mol. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.jacc.2018.11.033","article-title":"Heart Failure With Preserved Ejection Fraction and Diabetes: JACC State-of-the-Art Review","volume":"73","author":"McHugh","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1161\/CIRCRESAHA.110.223545","article-title":"Oxidative stress and diabetic complications","volume":"107","author":"Giacco","year":"2010","journal-title":"Circ. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3389\/fcvm.2020.00012","article-title":"Mitochondrial ROS Formation in the Pathogenesis of Diabetic Cardiomyopathy","volume":"7","author":"Kaludercic","year":"2020","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1113\/jphysiol.2007.135871","article-title":"Diabetes associated cell stress and dysfunction: Role of mitochondrial and non-mitochondrial ROS production and activity","volume":"583","author":"Newsholme","year":"2007","journal-title":"J. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Marino, F., Scalise, M., Cianflone, E., Salerno, L., Cappetta, D., Salerno, N., De Angelis, A., Torella, D., and Urbanek, K. (2021). Physical Exercise and Cardiac Repair: The Potential Role of Nitric Oxide in Boosting Stem Cell Regenerative Biology. Antioxidants, 10.","DOI":"10.3390\/antiox10071002"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1161\/CIRCRESAHA.116.306923","article-title":"Molecular and Cellular Mechanisms of Cardiovascular Disorders in Diabetes","volume":"118","author":"Shah","year":"2016","journal-title":"Circ. Res."},{"key":"ref_44","first-page":"5732956","article-title":"The Role of Oxidative Stress in Cardiac Disease: From Physiological Response to Injury Factor","volume":"2020","author":"Schipani","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3716","DOI":"10.1172\/JCI120849","article-title":"Mitochondrial dysfunction in pathophysiology of heart failure","volume":"128","author":"Zhou","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4112","DOI":"10.4161\/cc.8.24.10215","article-title":"Pseudo-DNA damage response in senescent cells","volume":"8","author":"Pospelova","year":"2009","journal-title":"Cell Cycle"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1096\/fj.00-0750fje","article-title":"Disruption of the plasminogen activator inhibitor 1 gene reduces the adiposity and improves the metabolic profile of genetically obese and diabetic ob\/ob mice","volume":"15","author":"Fujisawa","year":"2001","journal-title":"FASEB J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"336","DOI":"10.2337\/diabetes.53.2.336","article-title":"Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1","volume":"53","author":"Ma","year":"2004","journal-title":"Diabetes"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1007\/BF03402048","article-title":"Insulin continues to induce plasminogen activator inhibitor 1 gene expression in insulin-resistant mice and adipocytes","volume":"6","author":"Samad","year":"2000","journal-title":"Mol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/hr.2009.43","article-title":"Diabetes mellitus accelerates left ventricular diastolic dysfunction through activation of the renin-angiotensin system in hypertensive rats","volume":"32","author":"Fukui","year":"2009","journal-title":"Hypertens. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1093\/cvr\/cvs334","article-title":"Up-regulation of sarcoplasmic reticulum Ca2+ uptake leads to cardiac hypertrophy, contractile dysfunction and early mortality in mice deficient in CASQ2","volume":"98","author":"Kalyanasundaram","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_52","first-page":"394","article-title":"Boosting autophagy in the diabetic heart: A translational perspective","volume":"5","author":"Sciarretta","year":"2015","journal-title":"Cardiovasc. Diagn. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-physiol-021317-121427","article-title":"The Role of Autophagy in the Heart","volume":"80","author":"Sciarretta","year":"2018","journal-title":"Annu. Rev. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Cianflone, E., Torella, M., Biamonte, F., De Angelis, A., Urbanek, K., Costanzo, F.S., Rota, M., Ellison-Hughes, G.M., and Torella, D. (2020). Targeting Cardiac Stem Cell Senescence to Treat Cardiac Aging and Disease. Cells, 9.","DOI":"10.3390\/cells9061558"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1038\/s42003-021-02677-y","article-title":"In vitro CSC-derived cardiomyocytes exhibit the typical microRNA-mRNA blueprint of endogenous cardiomyocytes","volume":"4","author":"Scalise","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"CUTADAPT removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet. J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.12688\/f1000research.125325.1","article-title":"Librarian: A quality control tool to analyse sequencing library compositions","volume":"11","author":"Vashishtha","year":"2022","journal-title":"F1000Research"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: An efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0166-4328(01)00297-2","article-title":"Controlling the false discovery rate in behavior genetics research","volume":"125","author":"Benjamini","year":"2001","journal-title":"Behav. Brain Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Salvati, A., Gigantino, V., Nassa, G., Giurato, G., Alexandrova, E., Rizzo, F., Tarallo, R., and Weisz, A. (2019). The Histone Methyltransferase DOT1L Is a Functional Component of Estrogen Receptor Alpha Signaling in Ovarian Cancer Cells. 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