{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:25:32Z","timestamp":1760239532534,"version":"build-2065373602"},"reference-count":66,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,11,28]],"date-time":"2020-11-28T00:00:00Z","timestamp":1606521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgesellschaft","award":["MI-1146\/2-2"],"award-info":[{"award-number":["MI-1146\/2-2"]}]},{"name":"FoRUM (Ruhr-University Bochum)","award":["FoRUM F842R-2015"],"award-info":[{"award-number":["FoRUM F842R-2015"]}]},{"name":"German Foundation for Heart Research (DSHF)","award":["F07\/17"],"award-info":[{"award-number":["F07\/17"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Cardiovascular diseases are the number one cause of morbidity and mortality worldwide, but the underlying molecular mechanisms remain not well understood. Cardiomyopathies are primary diseases of the heart muscle and contribute to high rates of heart failure and sudden cardiac deaths. Here, we distinguished four different genetic cardiomyopathies based on gene expression signatures. In this study, RNA-Sequencing was used to identify gene expression signatures in myocardial tissue of cardiomyopathy patients in comparison to non-failing human hearts. Therefore, expression differences between patients with specific affected genes, namely LMNA (lamin A\/C), RBM20 (RNA binding motif protein 20), TTN (titin) and PKP2 (plakophilin 2) were investigated. We identified genotype-specific differences in regulated pathways, Gene Ontology (GO) terms as well as gene groups like secreted or regulatory proteins and potential candidate drug targets revealing specific molecular pathomechanisms for the four subtypes of genetic cardiomyopathies. Some regulated pathways are common between patients with mutations in RBM20 and TTN as the splice factor RBM20 targets amongst other genes TTN, leading to a similar response on pathway level, even though many differentially expressed genes (DEGs) still differ between both sample types. The myocardium of patients with mutations in LMNA is widely associated with upregulated genes\/pathways involved in immune response, whereas mutations in PKP2 lead to a downregulation of genes of the extracellular matrix. Our results contribute to further understanding of the underlying molecular pathomechanisms aiming for novel and better treatment of genetic cardiomyopathies.<\/jats:p>","DOI":"10.3390\/genes11121430","type":"journal-article","created":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T21:55:31Z","timestamp":1606686931000},"page":"1430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Distinct Myocardial Transcriptomic Profiles of Cardiomyopathies Stratified by the Mutant Genes"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4022-8531","authenticated-orcid":false,"given":"Katharina","family":"Sielemann","sequence":"first","affiliation":[{"name":"Erich and Hanna Klessmann Institute, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Centre NRW, Georgstrasse 11, D-32545 Bad Oeynhausen, Germany"},{"name":"Center for Biotechnology (CeBiTec), Bielefeld University, 33615 Bielefeld, Germany"},{"name":"Graduate School DILS, Bielefeld Institute for Bioinformatics Infrastructure (BIBI), Bielefeld University, 33615 Bielefeld, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zaher","family":"Elbeck","sequence":"additional","affiliation":[{"name":"Department of Medicine, Integrated Cardio Metabolic Centre (ICMC), Heart and Vascular Theme, Karolinska Institutet, 141 57 Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"G\u00e4rtner","sequence":"additional","affiliation":[{"name":"Erich and Hanna Klessmann Institute, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Centre NRW, Georgstrasse 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9202-2343","authenticated-orcid":false,"given":"Andreas","family":"Brodehl","sequence":"additional","affiliation":[{"name":"Erich and Hanna Klessmann Institute, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Centre NRW, Georgstrasse 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Stanasiuk","sequence":"additional","affiliation":[{"name":"Erich and Hanna Klessmann Institute, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Centre NRW, Georgstrasse 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2187-8715","authenticated-orcid":false,"given":"Henrik","family":"Fox","sequence":"additional","affiliation":[{"name":"Erich and Hanna Klessmann Institute, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Centre NRW, Georgstrasse 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9095-1277","authenticated-orcid":false,"given":"Lech","family":"Paluszkiewicz","sequence":"additional","affiliation":[{"name":"Erich and Hanna Klessmann Institute, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Centre NRW, Georgstrasse 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Tiesmeier","sequence":"additional","affiliation":[{"name":"Erich and Hanna Klessmann Institute, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Centre NRW, Georgstrasse 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Wlost","sequence":"additional","affiliation":[{"name":"Erich and Hanna Klessmann Institute, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Centre NRW, Georgstrasse 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Gummert","sequence":"additional","affiliation":[{"name":"Erich and Hanna Klessmann Institute, Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Centre NRW, Georgstrasse 11, D-32545 Bad Oeynhausen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1827-9914","authenticated-orcid":false,"given":"Stefan P.","family":"Albaum","sequence":"additional","affiliation":[{"name":"Center for Biotechnology (CeBiTec), Bielefeld University, 33615 Bielefeld, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janik","family":"Sielemann","sequence":"additional","affiliation":[{"name":"Center for Biotechnology (CeBiTec), Bielefeld University, 33615 Bielefeld, Germany"},{"name":"Graduate School DILS, Bielefeld Institute for Bioinformatics Infrastructure (BIBI), Bielefeld University, 33615 Bielefeld, 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Mol. Diagn."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.cardfail.2009.01.006","article-title":"Genetic evaluation of cardiomyopathy-A heart failure society of America practice guideline","volume":"15","author":"Hershberger","year":"2009","journal-title":"J. Card. Fail."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1056\/NEJMra0902923","article-title":"Inherited cardiomyopathies","volume":"364","author":"Watkins","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1093\/eurheartj\/ehu509","article-title":"Impact of genotype on clinical course in arrhythmogenic right ventricular dysplasia\/cardiomyopathy-associated mutation carriers","volume":"36","author":"Bhonsale","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/ejhg.2013.124","article-title":"Clinical utility gene card for: Arrhythmogenic right ventricular cardiomyopathy (ARVC)","volume":"22","author":"Rijdt","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Brodehl, A., Ebbinghaus, H., Deutsch, M.-A., Gummert, J., Gaertner, A., Ratnavadivel, S., and Milting, H. (2019). Human induced pluripotent stem-cell-derived cardiomyocytes as models for genetic cardiomyopathies. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184381"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e147","DOI":"10.1016\/j.jacc.2013.05.019","article-title":"2013 ACCF\/AHA guideline for the management of heart failure","volume":"62","author":"Yancy","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1093\/eurheartj\/ehq271","article-title":"Genetic counselling and testing in cardiomyopathies: A position statement of the European Society of Cardiology Working Group on myocardial and pericardial diseases","volume":"31","author":"Charron","year":"2010","journal-title":"Eur. Heart J."},{"key":"ref_9","first-page":"1120","article-title":"Adult heart transplant: Indications and outcomes","volume":"6","author":"Alraies","year":"2014","journal-title":"J. Thorac. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Towbin, J.A. (2014). Inherited cardiomyopathies. Circ. J., CJ\u201314.","DOI":"10.1253\/circj.CJ-14-0893"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s11886-013-0375-1","article-title":"Genetic evaluation of dilated cardiomyopathy","volume":"15","author":"Morales","year":"2013","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1093\/eurheartj\/ehl530","article-title":"Arrhythmogenic right ventricular cardiomyopathy: A \u2018final common pathway\u2019 that defines clinical phenotype","volume":"28","author":"Vatta","year":"2007","journal-title":"Eur. Heart J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13023-016-0407-1","article-title":"Arrhythmogenic cardiomyopathy","volume":"11","author":"Pilichou","year":"2016","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1002\/ejhf.1534","article-title":"Definition and treatment of arrhythmogenic cardiomyopathy: An updated expert panel report","volume":"21","author":"Elliott","year":"2019","journal-title":"Eur. J. Heart Fail."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/s41569-019-0200-7","article-title":"Molecular mechanisms of arrhythmogenic cardiomyopathy","volume":"16","author":"Austin","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1161\/CIRCRESAHA.117.309345","article-title":"Arrhythmogenic cardiomyopathy","volume":"121","author":"Corrado","year":"2017","journal-title":"Circ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"90","DOI":"10.15420\/AER.2016.4.3","article-title":"Arrhythmogenic cardiomyopathy: Electrical and structural phenotypes","volume":"5","author":"Akdis","year":"2016","journal-title":"Arrhythm. Electrophysiol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e301","DOI":"10.1016\/j.hrthm.2019.05.007","article-title":"2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy","volume":"16","author":"Towbin","year":"2019","journal-title":"Hear. Rhythm."},{"key":"ref_19","first-page":"504","article-title":"Filamin C truncation mutations are associated with arrhythmogenic dilated cardiomyopathy and changes in the cell-cell adhesion structures","volume":"4","author":"Begay","year":"2018","journal-title":"JACC: Clin. Electrophysiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e014628","DOI":"10.1161\/JAHA.119.014628","article-title":"Arrhythmogenic right ventricular cardiomyopathy: Characterization of left ventricular phenotype and differential diagnosis with dilated cardiomyopathy","volume":"9","author":"Cipriani","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/00045415-200109000-00005","article-title":"Arrhythmogenic right ventricular cardiomyopathy: Current diagnostic and management strategies","volume":"9","author":"Corrado","year":"2001","journal-title":"Cardiol. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1093\/eurheartj\/ehv727","article-title":"Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: A position statement of the ESC working group on myocardial and pericardial diseases","volume":"37","author":"Pinto","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_24","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":"2007","journal-title":"Eur. Heart J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1093\/eurheartj\/ehq025","article-title":"Diagnosis of arrhythmogenic right ventricular cardiomyopathy\/dysplasia: Proposed modification of the task force criteria","volume":"31","author":"Marcus","year":"2010","journal-title":"Eur. Heart J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1161\/CIRCULATIONAHA.109.905091","article-title":"Cardiac index is associated with brain aging","volume":"122","author":"Jefferson","year":"2010","journal-title":"Circulation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12859-018-2024-6","article-title":"MutScan: Fast detection and visualization of target mutations by scanning FASTQ data","volume":"19","author":"Chen","year":"2018","journal-title":"BMC Bioinform."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_29","unstructured":"Andrews, S. (2010). FastQC: A Quality Control. Tool for High. Throughout Sequence Data, Babraham Institute."},{"key":"ref_30","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_31","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":"2013","journal-title":"Bioinformatics"},{"key":"ref_32","first-page":"2122","article-title":"A step-by-step workflow for low-level analysis of single-cell RNA-seq data with Bioconductor","volume":"5","author":"Lun","year":"2016","journal-title":"F1000Research"},{"key":"ref_33","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_34","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/wics.147","article-title":"ggplot2","volume":"3","author":"Wickham","year":"2011","journal-title":"Wiley Interdiscip. Rev. Comput. Stat."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Chen, H., and Boutros, P.C. (2011). VennDiagram: A package for the generation of highly-customizable Venn and Euler diagrams in R. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-35"},{"key":"ref_36","first-page":"1","article-title":"Clust: Automatic extraction of optimal co-expressed gene clusters from gene expression data","volume":"19","author":"Kelly","year":"2018","journal-title":"Genome Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Luo, W., Friedman, M.S., Shedden, K., Hankenson, K.D., and Woolf, P.J. (2009). GAGE: Generally applicable gene set enrichment for pathway analysis. BMC Bioinform., 10.","DOI":"10.1186\/1471-2105-10-161"},{"key":"ref_38","first-page":"6","article-title":"Tutorial: RNA-seq differential expression & pathway analysis with Sailfish, DESeq2, GAGE, and Pathview","volume":"16755","author":"Turner","year":"2015","journal-title":"DIM"},{"key":"ref_39","unstructured":"Pages, H., Carlson, M., Falcon, S., Li, N.A., AnnotationDbi, P., and SQLForge, P. (2020, November 27). Annotation Database Interface; In R Package Version 1.52.0. Available online: https:\/\/bioconductor.org\/packages\/AnnotationDbi."},{"key":"ref_40","unstructured":"Carlson, M., Falcon, S., Pages, H., and Li, N. (2018). Org. Hs. Eg. Db: Genome Wide Annotation for Human. R Package Version 3.7.0, Springer."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1093\/bioinformatics\/btt285","article-title":"Pathview: An R\/Bioconductor package for pathway-based data integration and visualization","volume":"29","author":"Luo","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_42","unstructured":"Plotly Technologies Inc. (2020, November 27). Collaborative Data Science. Available online: https:\/\/plot.ly."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"eaag1166","DOI":"10.1126\/scitranslmed.aag1166","article-title":"The druggable genome and support for target identification and validation in drug development","volume":"9","author":"Finan","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/nrd892","article-title":"The druggable genome","volume":"1","author":"Hopkins","year":"2002","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1172\/jci.insight.126315","article-title":"Prelamin A mediates myocardial inflammation in dilated and HIV-associated cardiomyopathies","volume":"4","author":"Brayson","year":"2019","journal-title":"JCI Insight"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1152\/physiolgenomics.00094.2011","article-title":"Myocardial transcriptome analysis of human arrhythmogenic right ventricular cardiomyopathy","volume":"44","author":"Gaertner","year":"2012","journal-title":"Physiol. Genom."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Klauke, B., Gaertner-Rommel, A., Schulz, U., Kassner, A., Zu Knyphausen, E., Laser, T., Kececioglu, D., Paluszkiewicz, L., Blanz, U., and Sandica, E. (2017). High proportion of genetic cases in patients with advanced cardiomyopathy including a novel homozygous Plakophilin 2-gene mutation. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0189489"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1093\/eurjhf\/hfs119","article-title":"Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: Evidence supporting the concept of arrhythmogenic cardiomyopathy","volume":"14","author":"Asimaki","year":"2012","journal-title":"Eur. J. Heart Fail."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1080\/19491034.2018.1454168","article-title":"Causes and consequences of genomic instability in laminopathies: Replication stress and interferon response","volume":"9","author":"Graziano","year":"2018","journal-title":"Nucleus"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1023\/A:1015372407647","article-title":"Electron transport chain defects in heart failure","volume":"7","author":"Casademont","year":"2002","journal-title":"Heart Fail. Rev."},{"key":"ref_51","first-page":"85","article-title":"Mitochondrial gene expression and respiratory enzyme activities in cardiac diseases","volume":"1406","author":"Bornstein","year":"1998","journal-title":"Biochim. Biophys. Acta (BBA)-Bioenergy"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.bbamem.2007.07.014","article-title":"Desmosome structure, composition and function","volume":"1778","author":"Garrod","year":"2008","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ijcard.2019.12.002","article-title":"RNA sequencing-based transcriptome profiling of cardiac tissue implicates novel putative disease mechanisms in FLNC-associated arrhythmogenic cardiomyopathy","volume":"302","author":"Hall","year":"2020","journal-title":"Int. J. Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.trsl.2019.02.004","article-title":"Mutations in ILK, encoding integrin-linked kinase, are associated with arrhythmogenic cardiomyopathy","volume":"208","author":"Brodehl","year":"2019","journal-title":"Transl. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3109\/15419061.2014.906533","article-title":"Desmosomes in the heart: A review of clinical and mechanistic analyses","volume":"21","author":"Patel","year":"2014","journal-title":"Cell Commun. Adhes."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1016\/0024-3205(95)02179-M","article-title":"L-glutamate-induced changes in intracellular calcium oscillation frequency through non-classical glutamate receptor binding in cultured rat myocardial cells","volume":"57","author":"Winter","year":"1995","journal-title":"Life Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1093\/cvr\/cvw192","article-title":"A mutation in the glutamate-rich region of RNA-binding motif protein 20 causes dilated cardiomyopathy through missplicing of titin and impaired Frank-Starling mechanism","volume":"112","author":"Beqqali","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-13675-8","article-title":"Abnormal contractility in human heart myofibrils from patients with dilated cardiomyopathy due to mutations in TTN and contractile protein genes","volume":"7","author":"Vikhorev","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1126\/science.aaa5458","article-title":"Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy","volume":"349","author":"Hinson","year":"2015","journal-title":"Science"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/nrcardio.2017.190","article-title":"Role of titin in cardiomyopathy: From DNA variants to patient stratification","volume":"15","author":"Ware","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1111\/joim.12287","article-title":"Heart failure and Alzheimer\u2032s disease","volume":"277","author":"Cermakova","year":"2014","journal-title":"J. Intern. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.cardiores.2006.10.002","article-title":"The role of TGF-\u03b2; signaling in myocardial infarction and cardiac remodeling","volume":"74","author":"Bujak","year":"2007","journal-title":"Cardiovasc. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.cardiores.2004.10.005","article-title":"Regulatory mutations in transforming growth factor-\u03b23 gene cause arrhythmogenic right ventricular cardiomyopathy type 1","volume":"65","author":"Beffagna","year":"2005","journal-title":"Cardiovasc. Res."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Li, Q., and Lai, L. (2007). Prediction of potential drug targets based on simple sequence properties. BMC Bioinform., 8.","DOI":"10.1186\/1471-2105-8-353"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1007\/s000590050003","article-title":"The \u201cFinal Common Pathway\u201d hypothesis and inherited cardiovascular disease the role of Cytoskeletal proteins in dilated cardiomyopathy","volume":"25","author":"Bowles","year":"2000","journal-title":"Herz"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12864-018-5213-9","article-title":"Transcriptome analysis of human heart failure reveals dysregulated cell adhesion in dilated cardiomyopathy and activated immune pathways in ischemic heart failure","volume":"19","author":"Sweet","year":"2018","journal-title":"BMC Genom."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/12\/1430\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:38:48Z","timestamp":1760179128000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/12\/1430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,28]]},"references-count":66,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["genes11121430"],"URL":"https:\/\/doi.org\/10.3390\/genes11121430","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2020,11,28]]}}}