{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:29:07Z","timestamp":1760239747032,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:00:00Z","timestamp":1608249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/87556\/2012","SFRH\/BD\/96026\/2013"],"award-info":[{"award-number":["SFRH\/BD\/87556\/2012","SFRH\/BD\/96026\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundo Europeu de Desenvolvimento Regional (FEDER) and Programa Operacional Factores de Competitividade (COMPETE)","award":["UID\/IC\/00051\/2013"],"award-info":[{"award-number":["UID\/IC\/00051\/2013"]}]},{"name":"Fundo Europeu de Desenvolvimento Regional (FEDER)","award":["COMPETE 2020 \u2013 Programa Operacional Competitividade E Internacionaliza\u00e7\u00e3o (POCI)"],"award-info":[{"award-number":["COMPETE 2020 \u2013 Programa Operacional Competitividade E Internacionaliza\u00e7\u00e3o (POCI)"]}]},{"name":"Norte Portugal regional operational program (NORTE 2020), under the Portugal 2020 partnership agreement, through the European Regional Development Fund (ERDF)","award":["NORTE-01-0145-FEDER-000003"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000003"]}]},{"name":"European Structural And Investment Funds, Lisbon\u2019s regional operational program 2020","award":["NETDIAMOND (POCI-01-0145-FEDER-016385)"],"award-info":[{"award-number":["NETDIAMOND (POCI-01-0145-FEDER-016385)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study aims to provide new insights into transcriptome and miRome modifications occurring in cardiac reverse remodelling (RR) upon left ventricle pressure-overload relief in mice. Pressure-overload was established in seven-week-old C57BL\/6J-mice by ascending aortic constriction. A debanding (DEB) surgery was performed seven weeks later in half of the banding group (BA). Two weeks later, cardiac function was evaluated through hemodynamics and echocardiography, and the hearts were collected for histology and small\/bulk-RNA-sequencing. Pressure-overload relief was confirmed by the normalization of left-ventricle-end-systolic-pressure. DEB animals were separated into two subgroups according to the extent of cardiac remodelling at seven weeks and RR: DEB1 showed an incomplete RR phenotype confirmed by diastolic dysfunction persistence (E\/e\u2019 \u2265 16 ms) and increased myocardial fibrosis. At the same time, DEB2 exhibited normal diastolic function and fibrosis, presenting a phenotype closer to myocardial recovery. Nevertheless, both subgroups showed the persistence of cardiomyocytes hypertrophy. Notably, the DEB1 subgroup presented a more severe diastolic dysfunction at the moment of debanding than the DEB2, suggesting a different degree of cardiac remodelling. Transcriptomic and miRomic data, as well as their integrated analysis, revealed significant downregulation in metabolic and hypertrophic related pathways in DEB1 when compared to DEB2 group, including fatty acid \u03b2-oxidation, mitochondria L-carnitine shuttle, and nuclear factor of activated T-cells pathways. Moreover, extracellular matrix remodelling, glycan metabolism and inflammation-related pathways were up-regulated in DEB1. The presence of a more severe diastolic dysfunction at the moment of pressure overload-relief on top of cardiac hypertrophy was associated with an incomplete RR. Our transcriptomic approach suggests that a cardiac inflammation, fibrosis, and metabolic-related gene expression dysregulation underlies diastolic dysfunction persistence after pressure-overload relief, despite left ventricular mass regression, as echocardiographically confirmed.<\/jats:p>","DOI":"10.3390\/ijms21249687","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T11:42:09Z","timestamp":1608291729000},"page":"9687","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Degree of Cardiac Remodelling before Overload Relief Triggers Different Transcriptome and miRome Signatures during Reverse Remodelling (RR)\u2014Molecular Signature Differ with the Extent of RR"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3767-2559","authenticated-orcid":false,"given":"Patr\u00edcia G.","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Cardiovascular Research and Development Center, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"}]},{"given":"Daniela","family":"Miranda-Silva","sequence":"additional","affiliation":[{"name":"Cardiovascular Research and Development Center, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9229-1236","authenticated-orcid":false,"given":"Xidan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine, Integrated Cardio Metabolic Centre (ICMC), Heart and Vascular Theme, Karolinska Institutet, 171 77 Stockholm, Sweden"}]},{"given":"Cl\u00e1udia","family":"Sousa-Mendes","sequence":"additional","affiliation":[{"name":"Cardiovascular Research and Development Center, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9337-1860","authenticated-orcid":false,"given":"Ricardo","family":"Martins-Ferreira","sequence":"additional","affiliation":[{"name":"Cardiovascular Research and Development Center, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2073-7988","authenticated-orcid":false,"given":"Zaher","family":"Elbeck","sequence":"additional","affiliation":[{"name":"Department of Medicine, Integrated Cardio Metabolic Centre (ICMC), Heart and Vascular Theme, Karolinska Institutet, 171 77 Stockholm, Sweden"}]},{"given":"Adelino F.","family":"Leite-Moreira","sequence":"additional","affiliation":[{"name":"Cardiovascular Research and Development Center, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"},{"name":"Department of Cardiothoracic Surgery, S\u00e3o Jo\u00e3o Hospital Center, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8871-112X","authenticated-orcid":false,"given":"Ralph","family":"Kn\u00f6ll","sequence":"additional","affiliation":[{"name":"Department of Medicine, Integrated Cardio Metabolic Centre (ICMC), Heart and Vascular Theme, Karolinska Institutet, 171 77 Stockholm, Sweden"},{"name":"Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&amp;D, AstraZeneca, 431 50 Gothenburg, Sweden"}]},{"given":"In\u00eas","family":"Falc\u00e3o-Pires","sequence":"additional","affiliation":[{"name":"Cardiovascular Research and Development Center, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1093\/eurheartj\/ehm342","article-title":"Classification of the cardiomyopathies: A position statement from the European Society Of Cardiology Working Group on Myocardial and Pericardial Diseases","volume":"29","author":"Elliott","year":"2008","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/ejhf.592","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"18","author":"Ponikowski","year":"2016","journal-title":"Eur. J. Heart Fail."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.jcmg.2018.11.026","article-title":"Imaging and Impact of Myocardial Fibrosis in Aortic Stenosis","volume":"12","author":"Bing","year":"2019","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e007131","DOI":"10.1161\/CIRCIMAGING.117.007131","article-title":"Myocardial Fibrosis Predicts 10-Year Survival in Patients Undergoing Aortic Valve Replacement","volume":"11","author":"Herrmann","year":"2018","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1016\/j.jcmg.2016.10.007","article-title":"Myocardial Fibrosis and Cardiac Decompensation in Aortic Stenosis","volume":"10","author":"Chin","year":"2017","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1002\/ehf2.12451","article-title":"Causes and consequences of cardiac fibrosis in patients referred for surgical aortic valve replacement","volume":"6","author":"Galat","year":"2019","journal-title":"ESC Heart Fail."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.ejcts.2011.05.039","article-title":"Myocardial metabolism and diastolic function after aortic valve replacement for aortic stenosis: Influence of patient-prosthesis mismatch","volume":"41","author":"Mannacio","year":"2012","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Heather, L.C., Howell, N.J., Emmanuel, Y., Cole, M.A., Frenneaux, M.P., Pagano, D., and Clarke, K. (2011). Changes in cardiac substrate transporters and metabolic proteins mirror the metabolic shift in patients with aortic stenosis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026326"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"36904","DOI":"10.1038\/srep36904","article-title":"Integrated microRNA and messenger RNA analysis in aortic stenosis","volume":"6","author":"Coffey","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e004278","DOI":"10.1161\/CIRCHEARTFAILURE.117.004278","article-title":"MicroRNAs Associated With Reverse Left Ventricular Remodelling in Humans Identify Pathways of Heart Failure Progression","volume":"11","author":"Shah","year":"2018","journal-title":"Circ. Heart Fail."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4476","DOI":"10.1038\/s41598-017-04762-x","article-title":"Heart Failure and MEF2 Transcriptome Dynamics in Response to beta-Blockers","volume":"7","author":"Tobin","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/j.drudis.2013.07.025","article-title":"Pivotal role of microRNAs in cardiac physiology and heart failure","volume":"18","author":"Lourenco","year":"2013","journal-title":"Drug Discov. Today"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1016\/j.jacc.2014.01.050","article-title":"microRNAs in cardiovascular diseases: Current knowledge and the road ahead","volume":"63","author":"Condorelli","year":"2014","journal-title":"Am. J. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s12471-016-0815-9","article-title":"Animal models of heart failure with preserved ejection fraction","volume":"24","author":"Conceicao","year":"2016","journal-title":"Neth. Heart J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4435","DOI":"10.1038\/s41467-018-06639-7","article-title":"Cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure","volume":"9","author":"Nomura","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1161\/CIRCRESAHA.111.249433","article-title":"Analysis of transcriptome complexity through RNA sequencing in normal and failing murine hearts","volume":"109","author":"Lee","year":"2011","journal-title":"Circ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1093\/eurheartj\/ehr378","article-title":"Echocardiographic diastolic parameters and risk of atrial fibrillation: The Cardiovascular Health Study","volume":"33","author":"Rosenberg","year":"2012","journal-title":"Eur. Heart J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.cmet.2013.08.009","article-title":"The hypoxia-inducible microRNA cluster miR-199a\u223c214 targets myocardial PPAR\u03b4 and impairs mitochondrial fatty acid oxidation","volume":"18","author":"Leptidis","year":"2013","journal-title":"Cell Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.yjmcc.2020.08.015","article-title":"Exercise training reveals micro-RNAs associated with improved cardiac function and electrophysiology in rats with heart failure after myocardial infarction","volume":"148","author":"Ahmed","year":"2020","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1042\/CS20190866","article-title":"A tangled tale of microRNA and cardiac fibrosis","volume":"133","author":"Chandy","year":"2019","journal-title":"Clin. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e89169","DOI":"10.1172\/jci.insight.89169","article-title":"Myocardial microRNAs associated with reverse remodelling in human heart failure","volume":"2","author":"Sucharov","year":"2017","journal-title":"JCI Insight"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11151","DOI":"10.1073\/pnas.1401724111","article-title":"Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers","volume":"111","author":"Akat","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"17615","DOI":"10.1073\/pnas.1206432109","article-title":"Therapeutic inhibition of the miR-34 family attenuates pathological cardiac remodelling and improves heart function","volume":"109","author":"Bernardo","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.jcmg.2015.06.029","article-title":"Early Diastolic Strain Rate in Relation to Systolic and Diastolic Function and Prognosis in Aortic Stenosis","volume":"9","author":"Dahl","year":"2016","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1253\/circj.CJ-12-0446","article-title":"Evaluation of left ventricular diastolic function after valve replacement in aortic stenosis using exercise Doppler echocardiography","volume":"76","author":"Seo","year":"2012","journal-title":"Circ. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12947-020-0184-9","article-title":"Assessment of left ventricular diastolic function after Transcatheter aortic valve implantation in aortic stenosis patients by echocardiographic according to different guidelines","volume":"18","author":"Guo","year":"2020","journal-title":"J. Cardiovasc. Ultrasound"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zacchigna, S., Paldino, A., Falc\u00e3o-Pires, I., Daskalopoulos, E.P., Dal Ferro, M., Vodret, S., Lesizza, P., Cannat\u00e0, A., Miranda-Silva, D., and Louren\u00e7o, A.P. (2020). Toward standardization of echocardiography for the evaluation of left ventricular function in adult rodents: A position paper of the ESC Working Group on Myocardial Function. Cardiovasc. Res.","DOI":"10.1093\/cvr\/cvaa110"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1093\/cvr\/cvy141","article-title":"A novel method for high precision aortic constriction that allows for generation of specific cardiac phenotypes in mice","volume":"114","author":"Melleby","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/j.1748-1716.2011.02369.x","article-title":"A mouse model of reverse cardiac remodelling following banding-debanding of the ascending aorta","volume":"205","author":"Bjornstad","year":"2012","journal-title":"Acta Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1038\/s41598-018-21548-x","article-title":"Experimental modelling of cardiac pressure overload hypertrophy: Modified technique for precise, reproducible, safe and easy aortic arch banding-debanding in mice","volume":"8","author":"Merino","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1161\/CIRCULATIONAHA.119.041694","article-title":"Single-Cell Sequencing of Mouse Heart Immune Infiltrate in Pressure Overload-Driven Heart Failure Reveals Extent of Immune Activation","volume":"140","author":"Martini","year":"2019","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"50","DOI":"10.4250\/jcvi.2019.27.e4","article-title":"Differential Transcriptome Profile and Exercise Capacity in Cardiac Remodelling by Pressure Overload versus Volume Overload","volume":"27","author":"Kim","year":"2019","journal-title":"Int. J. Cardiovasc. Imaging"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1161\/CIRCRESAHA.113.301667","article-title":"Parsing good versus bad signaling pathways in the heart: Role of calcineurin-nuclear factor of activated T-cells","volume":"113","author":"Molkentin","year":"2013","journal-title":"Circ. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1111\/gtc.12055","article-title":"Angiotensin II-induced cardiac hypertrophy and fibrosis are promoted in mice lacking Fgf16","volume":"18","author":"Matsumoto","year":"2013","journal-title":"Genes Cells"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.healun.2009.07.022","article-title":"Ventricular unloading is associated with increased 20s proteasome protein expression in the myocardium","volume":"29","author":"Wohlschlaeger","year":"2010","journal-title":"J. Heart Lung Transplant."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2956","DOI":"10.1038\/s41598-019-39581-9","article-title":"Characterization of biventricular alterations in myocardial (reverse) remodelling in aortic banding-induced chronic pressure overload","volume":"9","author":"Hamdani","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s40119-019-0134-5","article-title":"Left Ventricular Diastolic Dysfunction and Transcatheter Aortic Valve Replacement Outcomes: A Review","volume":"8","author":"Bavry","year":"2019","journal-title":"Cardiol. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1161\/01.CIR.91.9.2353","article-title":"Normalization of diastolic dysfunction in aortic stenosis late after valve replacement","volume":"91","author":"Villari","year":"1995","journal-title":"Circulation"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/S0140-6736(06)68074-4","article-title":"Controversies in ventricular remodelling","volume":"367","author":"Opie","year":"2006","journal-title":"Lancet"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1152\/physiol.00043.2010","article-title":"The athlete\u2019s heart vs. the failing heart: Can signaling explain the two distinct outcomes?","volume":"26","author":"Weeks","year":"2011","journal-title":"Physiology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"H1402","DOI":"10.1152\/ajpheart.00696.2015","article-title":"Myocardial reverse remodelling: How far can we rewind?","volume":"310","author":"Rodrigues","year":"2016","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1161\/01.CIR.0000135591.37759.AF","article-title":"Altered titin expression, myocardial stiffness, and left ventricular function in patients with dilated cardiomyopathy","volume":"110","author":"Nagueh","year":"2004","journal-title":"Circulation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1517\/14728221003752743","article-title":"The apelinergic system: A promising therapeutic target","volume":"14","year":"2010","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1096\/fj.11-190728","article-title":"Thrombospondin-4 regulates fibrosis and remodelling of the myocardium in response to pressure overload","volume":"26","author":"Frolova","year":"2012","journal-title":"FASEB J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.jjcc.2013.09.013","article-title":"Periostin expression is upregulated and associated with myocardial fibrosis in human failing hearts","volume":"63","author":"Zhao","year":"2014","journal-title":"J. Cardiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/cvr\/cvt100","article-title":"Osteopontin-mediated myocardial fibrosis in heart failure: A role for lysyl oxidase?","volume":"99","author":"Lopez","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.cardiores.2006.09.011","article-title":"Toll-like receptor stimulation in cardiomyoctes decreases contractility and initiates an NF-kappaB dependent inflammatory response","volume":"72","author":"Boyd","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.cardiores.2006.10.002","article-title":"The role of TGF-beta signaling in myocardial infarction and cardiac remodelling","volume":"74","author":"Bujak","year":"2007","journal-title":"Cardiovasc. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e004351","DOI":"10.1161\/CIRCHEARTFAILURE.117.004351","article-title":"Load-Dependent Changes in Left Ventricular Structure and Function in a Pathophysiologically Relevant Murine Model of Reversible Heart Failure","volume":"11","author":"Weinheimer","year":"2018","journal-title":"Circ. Heart Fail."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.3389\/fimmu.2018.02651","article-title":"The Inflammatory Response to Ventricular Assist Devices","volume":"9","author":"Radley","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/ni.3704","article-title":"Mitochondria are the powerhouses of immunity","volume":"18","author":"Mills","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1042\/BCJ20170714","article-title":"Mitochondrial DNA as an inflammatory mediator in cardiovascular diseases","volume":"475","author":"Nakayama","year":"2018","journal-title":"Biochem. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/cvr\/cvw051","article-title":"Normalization of cardiac substrate utilization and left ventricular hypertrophy precede functional recovery in heart failure regression","volume":"110","author":"Byrne","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1161\/CIRCRESAHA.116.308030","article-title":"Chronic Heart Failure and Inflammation: What Do We Really Know?","volume":"119","author":"Dick","year":"2016","journal-title":"Circ. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1161\/CIRCULATIONAHA.115.020226","article-title":"Catabolic Defect of Branched-Chain Amino Acids Promotes Heart Failure","volume":"133","author":"Sun","year":"2016","journal-title":"Circulation"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s12933-019-0892-3","article-title":"Impaired branched chain amino acid oxidation contributes to cardiac insulin resistance in heart failure","volume":"18","author":"Uddin","year":"2019","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"18443","DOI":"10.1074\/jbc.M117.800839","article-title":"Loss of cardiac carnitine palmitoyltransferase 2 results in rapamycin-resistant, acetylation-independent hypertrophy","volume":"292","author":"Pereyra","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.cmet.2018.02.011","article-title":"Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence","volume":"27","author":"Rajman","year":"2018","journal-title":"Cell Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1161\/01.CIR.0000026392.80723.DC","article-title":"Downregulation of myocardial myocyte enhancer factor 2C and myocyte enhancer factor 2C-regulated gene expression in diabetic patients with nonischemic heart failure","volume":"106","author":"Razeghi","year":"2002","journal-title":"Circulation"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1161\/01.CIR.0000155257.33485.6D","article-title":"Cardiomyocyte stiffness in diastolic heart failure","volume":"111","author":"Borbely","year":"2005","journal-title":"Circulation"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Sherman","year":"2009","journal-title":"Nat. Protoc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/24\/9687\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:47:05Z","timestamp":1760179625000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/24\/9687"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,18]]},"references-count":61,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijms21249687"],"URL":"https:\/\/doi.org\/10.3390\/ijms21249687","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2020,12,18]]}}}