2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T4ea,Right ventricular failure drives both morbidity and mortality in pulmonary arterial hypertension (PAH), but the mechanism of transition from compensated right ventricle (cRV) to decompensated RV (dRV) is unknown, and some PAH patients develop dRV faster than others. We explored the role of RV cardiac myofibroblasts (cMFBs) on this transition utilizing 2 rat models: monocrotaline (MCT) versus the less inflammatory pulmonary artery banding (PAB); and 3 patient cohorts (n=81) of PAH versus group 2 pulmonary hypertension (PHT-2). We hypothesized that loss of UCP2 (uncoupling protein 2), critical for mitochondrial calcium (mCa We separated rat cRV from dRV based on catheterization and echocardiographic criteria and found a significant increase in cMFBs from MCT but not PAB RV (which decompensated much later than MCT RV). In isolated hearts, MCT RV contractility was lower in dRV but not in isolated cardiomyocytes (CMs), pointing to a non-CM cause. Mitochondrial respiration was lower in MCT dRV cMFBs than in control and cRV cFBs but increased in MCT-RV CMs. mCa Our data suggest that a change of cell identity (cFBs to cMFBs) in the RV is a driver of RV decompensation. TNF-α or rs659366 is a potential biomarker for early RV decompensation in PAH.31:Tb3b, BACKGROUND: Right ventricular failure drives both morbidity and mortality in pulmonary arterial hypertension (PAH), but the mechanism of transition from compensated right ventricle (cRV) to decompensated RV (dRV) is unknown, and some PAH patients develop dRV faster than others. METHODS: We explored the role of RV cardiac myofibroblasts (cMFBs) on this transition utilizing 2 rat models: monocrotaline (MCT) versus the less inflammatory pulmonary artery banding (PAB); and 3 patient cohorts (n=81) of PAH versus group 2 pulmonary hypertension (PHT-2). We hypothesized that loss of UCP2 (uncoupling protein 2), critical for mitochondrial calcium (mCa ++ ) regulation and cardiac fibroblasts (cFBs) differentiation to cMFBs, is associated with dRV; and that a loss-of-function UCP2 single nucleotide polymorphism (SNP; rs659366) may predict dRV in human PAH. RESULTS: We separated rat cRV from dRV based on catheterization and echocardiographic criteria and found a significant increase in cMFBs from MCT but not PAB RV (which decompensated much later than MCT RV). In isolated hearts, MCT RV contractility was lower in dRV but not in isolated cardiomyocytes (CMs), pointing to a non-CM cause. Mitochondrial respiration was lower in MCT dRV cMFBs than in control and cRV cFBs but increased in MCT–RV CMs. mCa ++ was progressively decreased from normal to MCT–cRV to dRV cMFBs, and the same was true for c(M)FBs (but not CMs) UCP2. Tumor necrosis factor alpha (TNF-α) decreased UCP2 mRNA/protein levels in RV cFBs but not RV CMs. In human PAH, but not PHT-2, dRVs had more cMFBs and less UCP2 than control and cRVs. Decreased UCP2 levels and rs659366 were associated with worse RV performance (tricuspid annular plane systolic excursion and cardiac index), even among patients with similar mean pulmonary arterial pressure. CONCLUSIONS: Our data suggest that a change of cell identity (cFBs to cMFBs) in the RV is a driver of RV decompensation. TNF-α or rs659366 is a potential biomarker for early RV decompensation in PAH. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Group 2 Pulmonary Hypertension: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Group 2 Pulmonary Hypertension (condition). Clinician-written summaries and actionable practice insights. 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In isolated hearts, MCT RV contractility was lower in dRV but not in isolated cardiomyocytes (CMs), pointing to a non-CM cause. Mitochondrial respiration was lower in MCT dRV cMFBs than in control and cRV cFBs but increased in MCT-RV CMs. mCa","abstract":"$30","keywords":["calcium","heart failure","hypertension, pulmonary","hypertrophy, right ventricular","myofibroblasts","tumor necrosis factor-alpha","uncoupling protein 2"],"pubmed_id":"41797703","conclusions":"","publication_date":"2026-03-09T00:00:00"},"crossref":{"DOI":"10.1161/circulationaha.125.078674","URL":"https://doi.org/10.1161/circulationaha.125.078674","ISSN":["0009-7322","1524-4539"],"link":[{"URL":"https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.125.078674","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"1494-1515","type":"journal-article","issue":"19","score":1,"title":["Critical Contribution of Cardiac Myofibroblasts in Right Ventricular Failure and the Role of UCP2 SNPs in the Predisposition to RV Decompensation in Pulmonary Arterial Hypertension"],"author":[{"given":"Yongneng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Medicine (Cardiology), Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada (Y.Z., J.P., A.H., Y.L., Y.-Y.Z., G.S., E.D.M.)."}]},{"given":"Sébastien","family":"Bonnet","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension and Vascular Biology Research Group CRIUCPQ, Department of Medicine, Laval University, Quebec, Canada (S.B., S.P., S.B.-B., S.-E.L.)."},{"name":"Institute for Lung Health, German Center for Lung Research (DZL), Cardio-Pulmonary Institute, Justus Liebig University Giessen, Giessen, Germany (S.B.)."}]},{"given":"Steeve","family":"Provencher","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension and Vascular Biology Research Group CRIUCPQ, Department of Medicine, Laval University, Quebec, Canada (S.B., S.P., S.B.-B., 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J.P., A.H., Y.L., Y.-Y.Z., G.S., E.D.M.)."}]},{"given":"Sandra","family":"Breuils-Bonnet","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension and Vascular Biology Research Group CRIUCPQ, Department of Medicine, Laval University, Quebec, Canada (S.B., S.P., S.B.-B., S.-E.L.)."}]},{"given":"Sarah-Eve","family":"Lemay","sequence":"additional","affiliation":[{"name":"Pulmonary Hypertension and Vascular Biology Research Group CRIUCPQ, Department of Medicine, Laval University, Quebec, Canada (S.B., S.P., S.B.-B., S.-E.L.)."}]},{"given":"Dawn E.","family":"Bowles","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University Medical Center, Durham, NC(D.E.B., M.M.P.)."}]},{"given":"Michelle","family":"Mendiola Pla","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University Medical Center, Durham, NC(D.E.B., M.M.P.)."}]},{"given":"Gopinath","family":"Sutendra","sequence":"additional","affiliation":[{"name":"Department of 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study with human observational cohorts; design label is approximate.","value_numeric":null},{"paper_doi":"10.1161/circulationaha.125.078674","tag_type":"warning","value":"Study language metadata indicates German (de-DE), though the full text is in English — no content concern, likely a metadata artifact.","value_numeric":null},{"paper_doi":"10.1161/circulationaha.125.078674","tag_type":"warning","value":"The human cohort n=81 spans three institutions and two disease groups; subgroup sizes for SNP genotyping analyses are small (e.g., n=4–10 per genotype category), which limits statistical power.","value_numeric":null},{"paper_doi":"10.1161/circulationaha.125.078674","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously — findings are compelling but require prospective multicenter validation before routine clinical UCP2 genotyping is adopted.","value_numeric":null},{"paper_doi":"10.1161/circulationaha.125.078674","tag_type":"warning","value":"The study design is mixed (animal mechanistic + small human cohorts); the level of evidence reflects the human cohort component, which is observational and cross-sectional.","value_numeric":null}],"summaries":{"what_studied":"Two rat PAH models (monocrotaline vs pulmonary artery banding) and three human cohorts (n=81; PAH vs group 2 PH) were used to test whether RV cardiac fibroblast-to-myofibroblast change and UCP2 variants predispose to the shift from compensated to decompensated right ventricle. cRV and dRV were defined by catheterization and echocardiography.","key_result":"In rats, decompensated MCT RV showed expansion of RV cardiac myofibroblasts, lower whole-heart RV contractility despite preserved isolated cardiomyocyte function, and reduced mitochondrial respiration in RV myofibroblasts with increased respiration in RV cardiomyocytes; these changes were not seen with PAB, which decompensated later. In patients, TNF-α or the UCP2 SNP rs659366 was identified as a potential early biomarker of RV decompensation in PAH.","limitations":"Human data were limited to three cohorts totaling n=81. Findings differed between MCT and PAB models, suggesting model-specific effects that may limit generalization.","practice_takeaway":"RV fibroblast-to-myofibroblast transition appears tied to RV failure in PAH, pointing to a non-cardiomyocyte driver of decompensation. 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