Featured Publications
Cardiac dopamine D1 receptor triggers ventricular arrhythmia in chronic heart failure
Yamaguchi T, Sumida TS, Nomura S, Satoh M, Higo T, Ito M, Ko T, Fujita K, Sweet ME, Sanbe A, Yoshimi K, Manabe I, Sasaoka T, Taylor MRG, Toko H, Takimoto E, Naito AT, Komuro I. Cardiac dopamine D1 receptor triggers ventricular arrhythmia in chronic heart failure. Nature Communications 2020, 11: 4364. PMID: 32868781, PMCID: PMC7459304, DOI: 10.1038/s41467-020-18128-x.Peer-Reviewed Original ResearchConceptsVentricular arrhythmiasDopamine D1 receptorsD1 receptorsChronic heart failureHeart failure patientsSustained ventricular tachycardiaNormal calcium handlingFailure patientsHeart failureModel miceVentricular tachycardiaPathophysiological roleCalcium handlingTherapeutic targetDopamine systemSingle-cell resolution analysisArrhythmiasD1RCardiomyocytesReceptorsTachycardiaPatientsMice
2019
High-throughput single-molecule RNA imaging analysis reveals heterogeneous responses of cardiomyocytes to hemodynamic overload
Satoh M, Nomura S, Harada M, Yamaguchi T, Ko T, Sumida T, Toko H, Naito AT, Takeda N, Tobita T, Fujita T, Ito M, Fujita K, Ishizuka M, Kariya T, Akazawa H, Kobayashi Y, Morita H, Takimoto E, Aburatani H, Komuro I. High-throughput single-molecule RNA imaging analysis reveals heterogeneous responses of cardiomyocytes to hemodynamic overload. Journal Of Molecular And Cellular Cardiology 2019, 128: 77-89. PMID: 30611794, DOI: 10.1016/j.yjmcc.2018.12.018.Peer-Reviewed Original ResearchConceptsTransverse aortic constrictionHemodynamic overloadCardiomyocyte sizeExpression levelsGene expressionHeart failure stageSingle-cell RNA sequencingSingle-molecule RNAMyosin heavy chain βSingle-cell quantitative PCRFetal gene expressionFetal gene programSingle-cell analysis methodsSingle-molecule fluorescenceHeart failureSingle-cell levelPressure overloadAortic constrictionHypertrophy stageCardiac hypertrophyIsolated cardiomyocytesMyh7 expressionTemporal regulationRNA sequencingFetal genes
2018
Cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure
Nomura S, Satoh M, Fujita T, Higo T, Sumida T, Ko T, Yamaguchi T, Tobita T, Naito AT, Ito M, Fujita K, Harada M, Toko H, Kobayashi Y, Ito K, Takimoto E, Akazawa H, Morita H, Aburatani H, Komuro I. Cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure. Nature Communications 2018, 9: 4435. PMID: 30375404, PMCID: PMC6207673, DOI: 10.1038/s41467-018-06639-7.Peer-Reviewed Original ResearchConceptsCardiac hypertrophyCardiomyocyte remodelingGene programHeart failurePressure overloadMorphological hypertrophyHeart functionHypertrophyP53 deletionEarly hypertrophyFunctional signaturesFunctional phenotypeLate hypertrophyP53 signalingTranscriptional signatureProgram activationMitochondrial inhibitionUnderlying mechanismCardiomyocyte identityCardiomyocytesMitochondrial activationRemodelingFailureTranscriptional programsActivation
2017
DNA single-strand break-induced DNA damage response causes heart failure
Higo T, Naito AT, Sumida T, Shibamoto M, Okada K, Nomura S, Nakagawa A, Yamaguchi T, Sakai T, Hashimoto A, Kuramoto Y, Ito M, Hikoso S, Akazawa H, Lee JK, Shiojima I, McKinnon PJ, Sakata Y, Komuro I. DNA single-strand break-induced DNA damage response causes heart failure. Nature Communications 2017, 8: 15104. PMID: 28436431, PMCID: PMC5413978, DOI: 10.1038/ncomms15104.Peer-Reviewed Original ResearchConceptsPressure overload-induced heart failureOverload-induced heart failureHeart failureSingle-strand breaksNF-κB signalingNew therapeutic strategiesSSB accumulationDDR activationInflammatory cytokinesTherapeutic strategiesUnrepaired single-strand breaksDNA damageDNA single-strand breaksCausative roleDNA damage responseGenetic deletionPathogenesisActivationPivotal roleFailureDamage responseHeartCritical roleCytokinesMice
2016
Activation of endothelial β-catenin signaling induces heart failure
Nakagawa A, Naito AT, Sumida T, Nomura S, Shibamoto M, Higo T, Okada K, Sakai T, Hashimoto A, Kuramoto Y, Oka T, Lee JK, Harada M, Ueda K, Shiojima I, Limbourg FP, Adams RH, Noda T, Sakata Y, Akazawa H, Komuro I. Activation of endothelial β-catenin signaling induces heart failure. Scientific Reports 2016, 6: 25009. PMID: 27146149, PMCID: PMC4857119, DOI: 10.1038/srep25009.Peer-Reviewed Original ResearchConceptsWnt/β-cateninHeart failureCardiac dysfunctionCa miceEndothelial cellsΒ-cateninEndothelial β-cateninProgressive cardiac dysfunctionCardiac endothelial cellsDegeneration of mitochondriaArterial endothelial cellsNeuregulin-ErbB signalingNeuregulin proteinΒ-catenin-dependent canonical WntEndothelial expressionIschemic diseasesTherapeutic targetDysfunctionMiceSustained activationFunction mutationsNeuregulin-ErbBT-tubulesCanonical WntConditional gain