Pulmonary pressure load shapes right ventricular molecular remodelling in dilated cardiomyopathy
- 1Center of Experimental Rheumatology, Department of Rheumatology, University Hospital of Zurich, University of Zurich, Zurich, Switzerland
Abstract
Right ventricular (RV) adaptation to pulmonary hypertension determines outcome in dilated cardiomyopathy (DCM), but the molecular mechanisms of the transition to decompensation remain unclear. We analysed RV tissue from explanted hearts of patients with end-stage DCM using single-nucleus RNA sequencing (n=21), mass spectrometry and Olink Reveal proteomics (both n=44), and integrated these molecular profiles with echocardiographic and right-heart catheterisation measures to identify molecular correlates of RV dysfunction. Mean pulmonary arterial pressure was the dominant correlate of RV transcriptional remodelling, particularly in cardiomyocytes, where higher pressure was associated with contractile remodelling, autophagy, vesicle trafficking and glucose metabolism. In contrast, RV decompensation was characterised by immune activation and reduced oxidative phosphorylation exclusively at the proteomic level. Integrative multi-omics factor analysis (MOFA) further identified fibrosis as the dominant molecular program shared across transcriptomic and proteomic layers. Together, these findings indicate molecular adaptation to pressure load and tissue fibrosis during progression towards RV failure.
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BibTeX
@misc{bonazza2026pulmonary,
title = {{Pulmonary pressure load shapes right ventricular molecular remodelling in dilated cardiomyopathy}},
author = {G. A. Bonazza and A. Paterek and A. Bogucka and W. Scibek-Rejmontowska and A. Laimbacher and P. Leszek and O. Distler and M. Maczewski and P. Blyszczuk and G. Kania},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.28.747817},
url = {https://www.biorxiv.org/content/10.64898/2026.08.28.747817v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Pulmonary pressure load shapes right ventricular molecular remodelling in dilated cardiomyopathy
AU - G. A. Bonazza
AU - A. Paterek
AU - A. Bogucka
AU - W. Scibek-Rejmontowska
AU - A. Laimbacher
AU - P. Leszek
AU - O. Distler
AU - M. Maczewski
AU - P. Blyszczuk
AU - G. Kania
PY - 2026
DA - 2026/08/28
PB - bioRxiv
DO - 10.64898/2026.08.28.747817
UR - https://www.biorxiv.org/content/10.64898/2026.08.28.747817v1
AB - Right ventricular (RV) adaptation to pulmonary hypertension determines outcome in dilated cardiomyopathy (DCM), but the molecular mechanisms of the transition to decompensation remain unclear. We analysed RV tissue from explanted hearts of patients with end-stage DCM using single-nucleus RNA sequencing (n=21), mass spectrometry and Olink Reveal proteomics (both n=44), and integrated these molecular profiles with echocardiographic and right-heart catheterisation measures to identify molecular correlates of RV dysfunction. Mean pulmonary arterial pressure was the dominant correlate of RV transcriptional remodelling, particularly in cardiomyocytes, where higher pressure was associated with contractile remodelling, autophagy, vesicle trafficking and glucose metabolism. In contrast, RV decompensation was characterised by immune activation and reduced oxidative phosphorylation exclusively at the proteomic level. Integrative multi-omics factor analysis (MOFA) further identified fibrosis as the dominant molecular program shared across transcriptomic and proteomic layers. Together, these findings indicate molecular adaptation to pressure load and tissue fibrosis during progression towards RV failure.
ER -