{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:05:07Z","timestamp":1792670707853,"version":"4.5.0"},"reference-count":70,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,9,12]],"date-time":"2018-09-12T00:00:00Z","timestamp":1536710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Right ventricular failure (RVF) remains the leading cause of death in pulmonary arterial hypertension (PAH). We investigated the transcriptomic signature of RVF in hemodynamically well-phenotyped monocrotaline (MCT)-treated, male, Sprague-Dawley rats with severe PAH and decompensated RVF (increased right ventricular (RV) end diastolic volume (EDV), decreased cardiac output (CO), tricuspid annular plane systolic excursion (TAPSE) and ventricular-arterial decoupling). RNA sequencing revealed 2547 differentially regulated transcripts in MCT-RVF RVs. Multiple enriched gene ontology (GO) terms converged on mitochondria\/metabolism, fibrosis, inflammation, and angiogenesis. The mitochondrial transcriptomic pathway is the most affected in RVF, with 413 dysregulated genes. Downregulated genes included TFAM (\u22120.45-fold), suggesting impaired mitochondrial biogenesis, CYP2E1 (\u22123.8-fold), a monooxygenase which when downregulated increases oxidative stress, dehydrogenase\/reductase 7C (DHRS7C) (\u22122.8-fold), consistent with excessive autonomic activation, and polypeptide N-acetyl-galactose-aminyl-transferase 13 (GALNT13), a known pulmonary hypertension (PH) biomarker (\u22122.7-fold). The most up-regulated gene encodes Periostin (POSTN; 4.5-fold), a matricellular protein relevant to fibrosis. Other dysregulated genes relevant to fibrosis include latent-transforming growth factor beta-binding protein 2 (LTBP2), thrombospondin4 (THBS4). We also identified one dysregulated gene relevant to all disordered transcriptomic pathways, ANNEXIN A1. This anti-inflammatory, phospholipid-binding mediator, is a putative target for therapy in RVF-PAH. Comparison of expression profiles in the MCT-RV with published microarray data from the RV of pulmonary artery-banded mice and humans with bone morphogenetic protein receptor type 2 (BMPR2)-mutations PAH reveals substantial conservation of gene dysregulation, which may facilitate clinical translation of preclinical therapeutic and biomarkers studies. Transcriptomics reveals the molecular fingerprint of RVF to be heavily characterized by mitochondrial dysfunction, fibrosis and inflammation.<\/jats:p>","DOI":"10.3390\/ijms19092730","type":"journal-article","created":{"date-parts":[[2018,9,12]],"date-time":"2018-09-12T10:26:36Z","timestamp":1536747996000},"page":"2730","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Transcriptomic Signature of Right Ventricular Failure in Experimental Pulmonary Arterial Hypertension: Deep Sequencing Demonstrates Mitochondrial, Fibrotic, Inflammatory and Angiogenic Abnormalities"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1745-6445","authenticated-orcid":false,"given":"Francois","family":"Potus","sequence":"first","affiliation":[{"name":"Department of Medicine, Queen\u2019s University, Kingston, ON K7L3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles Colin Thomas","family":"Hindmarch","sequence":"additional","affiliation":[{"name":"Queen\u2019s Cardiopulmonary Unit (QCPU), Translational Institute of Medicine (TIME), Department of Medicine, Queen\u2019s University, Kingston, ON K7L3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly J.","family":"Dunham-Snary","sequence":"additional","affiliation":[{"name":"Department of Medicine, Queen\u2019s University, Kingston, ON K7L3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Stafford","sequence":"additional","affiliation":[{"name":"Centre for Advanced Computing, Queen\u2019s University, Kingston, ON K7L3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1106-3202","authenticated-orcid":false,"given":"Stephen L.","family":"Archer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Queen\u2019s University, Kingston, ON K7L3N6, Canada"},{"name":"Queen\u2019s Cardiopulmonary Unit (QCPU), Translational Institute of Medicine (TIME), Department of Medicine, Queen\u2019s University, Kingston, ON K7L3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1183\/09059180.00006511","article-title":"The role of the right ventricle in pulmonary arterial hypertension","volume":"20","year":"2011","journal-title":"Eur. 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