Pulmonary pressure load shapes right ventricular molecular remodelling in dilated cardiomyopathy
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…
The molecular changes in the right ventricle (RV) of patients with dilated cardiomyopathy (DCM) are largely driven by the pressure exerted by the pulmonary arteries (PA). This pressure load shapes right ventricular molecular remodeling, especially in cardiomyocytes. In these cells, higher pulmonary arterial pressure is linked to contractile remodeling, autophagy, vesicle trafficking, and glucose metabolism.
Conversely, right ventricular decompensation is marked by immune activation and reduced oxidative phosphorylation, as revealed by proteomic analysis. When the molecular profiles of both transcriptomics and proteomics are combined through integrative multi-omics factor analysis, fibrosis emerges as the primary molecular program shared between these layers.
The study concludes that the RV undergoes adaptive remodeling in response to pressure load and experiences tissue fibrosis as it progresses towards failure.
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