Systems biology approaches investigating mitochondrial dysfunction in cyanotic heart disease: a systematic reviewResearch in context
Summary: Background: Cyanotic congenital heart disease (CCHD) affects over 3 million individuals globally and can progress to heart failure. Mitochondrial dysfunction is well established in adult heart failure and is also a central feature of CCHD. CCHD cyanosis itself contributes to further mitoch...
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Elsevier
2025-08-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S235239642500283X |
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| author | Malak Elbatarny Yu Tong Lu Mostin Hu John Coles Seema Mital Amanda Ross-White Osami Honjo David J. Barron Anthony O. Gramolini |
| author_facet | Malak Elbatarny Yu Tong Lu Mostin Hu John Coles Seema Mital Amanda Ross-White Osami Honjo David J. Barron Anthony O. Gramolini |
| author_sort | Malak Elbatarny |
| collection | DOAJ |
| description | Summary: Background: Cyanotic congenital heart disease (CCHD) affects over 3 million individuals globally and can progress to heart failure. Mitochondrial dysfunction is well established in adult heart failure and is also a central feature of CCHD. CCHD cyanosis itself contributes to further mitochondrial dysfunction. Systems biology methods detail the epigenomic, transcriptomic, and metabolomic profile of biological samples. This systematic review highlights CCHD systems biology literature related to mitochondrial dysfunction. Methods: OVID/Medline was searched between January 2010 and June 2025. Studies implementing untargeted systems biology methods in CCHD tissue or plasma were included. Genes with differential expression between CCHD and unaffected controls were pooled and analysed using GO term functional enrichment for pathway analysis, transcription factor and kinase enrichment, and metabolic pathways. Findings: From 31 included studies (genomic: n = 5, epigenomic: n = 3, transcriptomic: n = 23, proteomic: n = 2, metabolomic: n = 3, lipidomic: n = 1), we identified 8 pathogenic/likely pathogenic single nucleotide polymorphisms, 73 differentially methylated genes, 4170 differentially expressed genes, 173 differentially expressed proteins between CCHD versus unaffected controls. Several genes involved in mitochondrial respiratory chain (NDUFV1, NDUFV2, NDUFA5, NDUFS3, COX5A, COQ7) were identified. Interpretation: CCHD pathogenesis and progression are associated with mitochondrial dysfunction through changes in metabolism, fission, and fusion. Funding: Vanier CIHR Scholarship, UHN Research Studentship, and Ontario Graduate Scholarship. Translational Biology and Engineering Program seed operating funds and research funding from the Heart and Stroke Foundation of Canada. |
| format | Article |
| id | doaj-art-09f4f6d48c4d4f76bc5e19a69ec5e897 |
| institution | Matheson Library |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj-art-09f4f6d48c4d4f76bc5e19a69ec5e8972025-07-13T04:54:32ZengElsevierEBioMedicine2352-39642025-08-01118105839Systems biology approaches investigating mitochondrial dysfunction in cyanotic heart disease: a systematic reviewResearch in contextMalak Elbatarny0Yu Tong Lu1Mostin Hu2John Coles3Seema Mital4Amanda Ross-White5Osami Honjo6David J. Barron7Anthony O. Gramolini8Division of Cardiac Surgery, University of Toronto, 200 Elizabeth St., Toronto, ON, M5G 2C4, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Medical Sciences Building, 3rd Floor, 1 King's College Circle, Toronto, ON, M5S 1A8, CanadaTemerty School of Medicine, University of Toronto, 1 King's College Cir, Toronto, ON, M5S 3K3, CanadaDepartment of Physiology, Faculty of Medicine, University of Toronto, Medical Sciences Building, 3rd Floor, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada; Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, 661 University Ave, 14th Floor, Toronto, ON, M5G 1M1 CanadaDivision of Cardiac Surgery, University of Toronto, 200 Elizabeth St., Toronto, ON, M5G 2C4, CanadaTemerty School of Medicine, University of Toronto, 1 King's College Cir, Toronto, ON, M5S 3K3, Canada; Division of Cardiology, Department of Pediatrics, University of Toronto, 555 University Avenue, Black Wing Room 1436, Toronto, ON, M5G 1X8, Canada; Genetics and Genome Biology Program, The Hospital for Sick Children, 686 Bay St, Toronto, ON, M5G 0A4, CanadaDepartment of Health Sciences, Queen's University, Botterell Hall, 6th Floor, Room 650, 18 Stuart Street, Kingston, ON, K7L 3N6, CanadaDivision of Cardiac Surgery, University of Toronto, 200 Elizabeth St., Toronto, ON, M5G 2C4, CanadaDivision of Cardiac Surgery, University of Toronto, 200 Elizabeth St., Toronto, ON, M5G 2C4, Canada; Corresponding author. Guy's and St Thomas' NHS Foundation Trust, Westminster Bridge Rd, London SE1 7EH, United Kingdom.Department of Physiology, Faculty of Medicine, University of Toronto, Medical Sciences Building, 3rd Floor, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada; Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, 661 University Ave, 14th Floor, Toronto, ON, M5G 1M1 Canada; Corresponding author. Translational Biology & Engineering Program, 661 University Ave, 14TH Floor, Rm 1437, Toronto, ON, M5G 1M1, Canada.Summary: Background: Cyanotic congenital heart disease (CCHD) affects over 3 million individuals globally and can progress to heart failure. Mitochondrial dysfunction is well established in adult heart failure and is also a central feature of CCHD. CCHD cyanosis itself contributes to further mitochondrial dysfunction. Systems biology methods detail the epigenomic, transcriptomic, and metabolomic profile of biological samples. This systematic review highlights CCHD systems biology literature related to mitochondrial dysfunction. Methods: OVID/Medline was searched between January 2010 and June 2025. Studies implementing untargeted systems biology methods in CCHD tissue or plasma were included. Genes with differential expression between CCHD and unaffected controls were pooled and analysed using GO term functional enrichment for pathway analysis, transcription factor and kinase enrichment, and metabolic pathways. Findings: From 31 included studies (genomic: n = 5, epigenomic: n = 3, transcriptomic: n = 23, proteomic: n = 2, metabolomic: n = 3, lipidomic: n = 1), we identified 8 pathogenic/likely pathogenic single nucleotide polymorphisms, 73 differentially methylated genes, 4170 differentially expressed genes, 173 differentially expressed proteins between CCHD versus unaffected controls. Several genes involved in mitochondrial respiratory chain (NDUFV1, NDUFV2, NDUFA5, NDUFS3, COX5A, COQ7) were identified. Interpretation: CCHD pathogenesis and progression are associated with mitochondrial dysfunction through changes in metabolism, fission, and fusion. Funding: Vanier CIHR Scholarship, UHN Research Studentship, and Ontario Graduate Scholarship. Translational Biology and Engineering Program seed operating funds and research funding from the Heart and Stroke Foundation of Canada.http://www.sciencedirect.com/science/article/pii/S235239642500283XSystems biologyMitochondriaCyanotic congenital heart diseaseMulti-omicsBioinformatics |
| spellingShingle | Malak Elbatarny Yu Tong Lu Mostin Hu John Coles Seema Mital Amanda Ross-White Osami Honjo David J. Barron Anthony O. Gramolini Systems biology approaches investigating mitochondrial dysfunction in cyanotic heart disease: a systematic reviewResearch in context EBioMedicine Systems biology Mitochondria Cyanotic congenital heart disease Multi-omics Bioinformatics |
| title | Systems biology approaches investigating mitochondrial dysfunction in cyanotic heart disease: a systematic reviewResearch in context |
| title_full | Systems biology approaches investigating mitochondrial dysfunction in cyanotic heart disease: a systematic reviewResearch in context |
| title_fullStr | Systems biology approaches investigating mitochondrial dysfunction in cyanotic heart disease: a systematic reviewResearch in context |
| title_full_unstemmed | Systems biology approaches investigating mitochondrial dysfunction in cyanotic heart disease: a systematic reviewResearch in context |
| title_short | Systems biology approaches investigating mitochondrial dysfunction in cyanotic heart disease: a systematic reviewResearch in context |
| title_sort | systems biology approaches investigating mitochondrial dysfunction in cyanotic heart disease a systematic reviewresearch in context |
| topic | Systems biology Mitochondria Cyanotic congenital heart disease Multi-omics Bioinformatics |
| url | http://www.sciencedirect.com/science/article/pii/S235239642500283X |
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