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Right ventricle (RV) function is known to be a major predictor of sustained cardiac health in these patients; thus, by elucidating the divergent profiles between CHD and the control through tissue analysis, this study aims to identify new avenues of investigation into the mechanisms surrounding reduced RV function. Transcriptomic profiling, in-silico deconvolution and functional network analysis were conducted on RV biopsies, identifying an increase in the mitochondrial dysfunction genes RPPH1 and RMPR (padj = 4.67 \u00d7 10\u2212132, 2.23 \u00d7 10\u2212107), the cytotoxic T-cell markers CD8a, LAGE3 and CD49a (p = 0.0006, p &lt; 0.0001, and p = 0.0118) and proinflammatory caspase-1 (p = 0.0055) in CHD. Gene-set enrichment identified mitochondrial dysfunctional pathways, predominately changes within oxidative phosphorylation processes. The negative regulation of mitochondrial functions and metabolism was identified in the network analysis, with dysregulation of the mitochondrial complex formation. A histological analysis confirmed an increase in cellular bodies in the CHD RV tissue and positive staining for both CD45 and CD8, which was absent in the control. The deconvolution of bulk RNAseq data suggests a reduction in CD4+ T cells (p = 0.0067) and an increase in CD8+ T cells (p = 0.0223). The network analysis identified positive regulation of the immune system and cytokine signalling clusters in the inflammation functional network, as there were lymphocyte activation and leukocyte differentiation. Utilising RV tissue from paediatric patients undergoing CHD cardiac surgery, this study identifies dysfunctional mitochondrial pathways and an increase in inflammatory T-cell presence prior to reparative surgery.<\/jats:p>","DOI":"10.3390\/ijms25137487","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T14:40:50Z","timestamp":1720449650000},"page":"7487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Altered Inflammatory State and Mitochondrial Function Identified by Transcriptomics in Paediatric Congenital Heart Patients Prior to Surgical Repair"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7436-3873","authenticated-orcid":false,"given":"Francesca","family":"Bartoli-Leonard","sequence":"first","affiliation":[{"name":"Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol BS8 1UD, UK"},{"name":"Bristol Heart Institute, University Hospital Bristol and Weston NHS Foundation Trust, Bristol BS2 8ED, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4749-6325","authenticated-orcid":false,"given":"Amy G.","family":"Harris","sequence":"additional","affiliation":[{"name":"Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol BS8 1UD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Saunders","sequence":"additional","affiliation":[{"name":"Bristol Heart Institute, University Hospital Bristol and Weston NHS Foundation Trust, Bristol BS2 8ED, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Madden","sequence":"additional","affiliation":[{"name":"Bristol Heart Institute, University Hospital Bristol and Weston NHS Foundation Trust, Bristol BS2 8ED, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"Cherrington","sequence":"additional","affiliation":[{"name":"Bristol Heart Institute, University Hospital Bristol and Weston NHS Foundation Trust, Bristol BS2 8ED, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1606-8184","authenticated-orcid":false,"given":"Karen","family":"Sheehan","sequence":"additional","affiliation":[{"name":"Bristol Heart Institute, University Hospital Bristol and Weston NHS Foundation Trust, Bristol BS2 8ED, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Baquedano","sequence":"additional","affiliation":[{"name":"Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol BS8 1UD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Parolari","sequence":"additional","affiliation":[{"name":"Bristol Heart Institute, University Hospital Bristol and Weston NHS Foundation Trust, Bristol BS2 8ED, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Bamber","sequence":"additional","affiliation":[{"name":"North Bristol NHS Trust, Westbury on Trym, Bristol BS10 5NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Caputo","sequence":"additional","affiliation":[{"name":"Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol BS8 1UD, UK"},{"name":"Bristol Heart Institute, University Hospital Bristol and Weston NHS Foundation Trust, Bristol BS2 8ED, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1053\/j.pcsu.2014.01.006","article-title":"Reoperations for pediatric and congenital heart disease: An analysis of the Society of Thoracic Surgeons (STS) congenital heart surgery database","volume":"17","author":"Jacobs","year":"2014","journal-title":"Semin. 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