Transcriptional changes of the extracellular matrix in chronic thromboembolic pulmonary hypertension govern right ventricle remodeling and recovery
Chronic thromboembolic pulmonary hypertension (CTEPH) leads to progressive right ventricular (RV) dysfunction. Pulmonary endarterectomy (PEA) is an established treatment for these patients; however, the molecular mechanisms underlying RV remodeling and recovery remain poorly understood. Here we show that RNA sequencing and histological analysis of RV free wall and septal biopsies from patients with CTEPH reveal extracellular matrix enrichment and cytoskeletal remodeling before PEA. These changes were consistent across an exploratory and confirmatory cohort. Post-PEA samples showed reversal of both histological and transcriptional abnormalities. Key signaling molecules-ANKRD1, IL7R and SERPINE1-were implicated in fibrotic and proliferative pathways, as confirmed in human tissues and experimental models. Our findings identify a reversible gene expression and structural remodeling signature in the RV, linking hemodynamic unloading with molecular recovery. These insights suggest potential therapeutic targets to modulate maladaptive RV remodeling in CTEPH and improve outcomes beyond surgical intervention.
Authors
- Przemysław Leszek (ORCID: https://orcid.org/0000-0003-4529-2687)
- Dimitri Grün (ORCID: https://orcid.org/0000-0002-8668-636X)
- Christian W. Hamm (ORCID: https://orcid.org/0000-0001-6763-4161)
- Christoph Liebetrau (ORCID: https://orcid.org/0000-0002-5499-7024)
- Werner Seeger (ORCID: https://orcid.org/0000-0003-1946-0894)
- Christian Troidl (ORCID: https://orcid.org/0000-0002-5574-9786)
- Peter Dorfmüller (ORCID: https://orcid.org/0000-0003-2499-6829)
- Péter Ferdinandy (ORCID: https://orcid.org/0000-0002-6424-6806)
- Baktybek Kojonazarov (ORCID: https://orcid.org/0000-0002-3252-359X)
- Ralph T. Schermuly (ORCID: https://orcid.org/0000-0002-5167-6970)
- Edda Spiekerkoetter (ORCID: https://orcid.org/0000-0002-3868-5186)
- Jochen Wilhelm (ORCID: https://orcid.org/0000-0001-5544-9647)
- Christoph B. Wiedenroth (ORCID: https://orcid.org/0000-0003-0065-3426)
- Prakash Chelladurai (ORCID: https://orcid.org/0000-0002-8258-5115)
- Soni Savai Pullamsetti (ORCID: https://orcid.org/0000-0003-0440-8831)
- Holger Nef (ORCID: https://orcid.org/0000-0002-2823-3928)
- Norbert Weißmann (ORCID: https://orcid.org/0000-0003-2675-3871)
- Zoltán V. Varga (ORCID: https://orcid.org/0000-0002-2758-0784)
- Carsten Kuenne (ORCID: https://orcid.org/0000-0001-8013-5906)
- Till Keller (ORCID: https://orcid.org/0000-0002-0895-6491)
- Stefan Günther (ORCID: https://orcid.org/0000-0002-5594-4549)
- Stanislav Keranov (ORCID: https://orcid.org/0000-0002-4379-4424)
- Leili Jafari (ORCID: https://orcid.org/0000-0001-6025-2734)
- Hossein Ardeschir Ghofrani (ORCID: https://orcid.org/0000-0002-2029-4419)
- Stefan Guth (ORCID: https://orcid.org/0000-0003-2238-9574)
- Oliver Dörr (ORCID: https://orcid.org/0000-0003-4526-6956)
- Mario Boehm (ORCID: https://orcid.org/0000-0003-4070-438X)
- Eckhard Mayer
- Steffen Kriechbaum
- A Spath
- Anoop V. Cherian
Institutions
- Semmelweis University (HU)
- Justus-Liebig-Universität Gießen (DE)
- Cardiovascular Institute of the South (US)
- Max Planck Institute for Heart and Lung Research (DE)
- German Centre for Cardiovascular Research (DE)
- Kerckhoff Klinik (DE)
- Institute of Cardiology (PL)
- Momentum Research (US)
- Cardio-Pulmonary Institute (DE)
- Stanford University (US)
Publication Details
- Journal
- Nature Cardiovascular Research
- Published
- 2025-07-04
- DOI
- https://doi.org/10.1038/s44161-025-00672-8
- Citations
- 3
- Primary Topic
- Pulmonary Hypertension Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 4.56