Attractor landscape analysis of the cardiac signaling network reveals mechanism-based therapeutic strategies for heart failure

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dc.contributor.authorPark, Daebeonko
dc.contributor.authorLee, Ho-Sungko
dc.contributor.authorKang, Jun Hyukko
dc.contributor.authorKim, Seon-Myeongko
dc.contributor.authorGong, Jeong-Ryeolko
dc.contributor.authorCho, Kwang-Hyunko
dc.date.accessioned2018-08-20T07:55:05Z-
dc.date.available2018-08-20T07:55:05Z-
dc.date.created2018-06-19-
dc.date.created2018-06-19-
dc.date.issued2018-06-
dc.identifier.citationJOURNAL OF MOLECULAR CELL BIOLOGY, v.10, no.3, pp.180 - 194-
dc.identifier.issn1674-2788-
dc.identifier.urihttp://hdl.handle.net/10203/244908-
dc.description.abstractApoptosis and hypertrophy of cardiomyocytes are the primary causes of heart failure (HF), a global leading cause of death, and are regulated through the complicated intracellular signaling network, limiting the development of effective treatments due to its complexity. To identify effective therapeutic strategies for HF at a system level, we develop a large-scale comprehensive mathematical model of the cardiac signaling network by integrating all available experimental evidence. Attractor landscape analysis of the network model identifies distinct sets of control nodes that effectively suppress apoptosis and hypertrophy of cardiomyocytes under ischemic or pressure overload-induced HF, the two major types of HF. Intriguingly, our system-level analysis suggests that intervention of these control nodes may increase the efficacy of clinical drugs for HF and, of most importance, different combinations of control nodes are suggested as potentially effective candidate drug targets depending on the types of HF. Our study provides a systematic way of developing mechanism-based therapeutic strategies for HF.-
dc.languageEnglish-
dc.publisherOXFORD UNIV PRESS-
dc.subjectEMBRYONIC STEM-CELLS-
dc.subjectMYOCARDIAL-INFARCTION-
dc.subjectRAT CARDIOMYOCYTES-
dc.subjectPROTEIN-KINASE-
dc.subjectGROWTH-FACTOR-
dc.subjectISCHEMIA/REPERFUSION INJURY-
dc.subjectPRESSURE-OVERLOAD-
dc.subjectSYSTEMS BIOLOGY-
dc.subjectKAPPA-B-
dc.subjectHYPERTROPHY-
dc.titleAttractor landscape analysis of the cardiac signaling network reveals mechanism-based therapeutic strategies for heart failure-
dc.typeArticle-
dc.identifier.wosid000439707300002-
dc.identifier.scopusid2-s2.0-85051006992-
dc.type.rimsART-
dc.citation.volume10-
dc.citation.issue3-
dc.citation.beginningpage180-
dc.citation.endingpage194-
dc.citation.publicationnameJOURNAL OF MOLECULAR CELL BIOLOGY-
dc.identifier.doi10.1093/jmcb/mjy019-
dc.contributor.localauthorCho, Kwang-Hyun-
dc.contributor.nonIdAuthorPark, Daebeon-
dc.contributor.nonIdAuthorKim, Seon-Myeong-
dc.description.isOpenAccessN-
dc.type.journalArticleArticle-
dc.subject.keywordAuthorheart failure-
dc.subject.keywordAuthormathematical modeling-
dc.subject.keywordAuthorcardiac signaling network-
dc.subject.keywordAuthorsystems analysis-
dc.subject.keywordAuthordisease mechanism-
dc.subject.keywordAuthormechanism-based therapeutic strategy-
dc.subject.keywordAuthorsystems biology-
dc.subject.keywordPlusEMBRYONIC STEM-CELLS-
dc.subject.keywordPlusMYOCARDIAL-INFARCTION-
dc.subject.keywordPlusRAT CARDIOMYOCYTES-
dc.subject.keywordPlusPROTEIN-KINASE-
dc.subject.keywordPlusGROWTH-FACTOR-
dc.subject.keywordPlusISCHEMIA/REPERFUSION INJURY-
dc.subject.keywordPlusPRESSURE-OVERLOAD-
dc.subject.keywordPlusSYSTEMS BIOLOGY-
dc.subject.keywordPlusKAPPA-B-
dc.subject.keywordPlusHYPERTROPHY-
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