Metrics of left ventricular active relaxation reflect proteomic myocardial remodelling and reverse remodelling
Introduction Pressure overload (PO) induces adverse myocardial remodelling, whereas efficient pressure unloading interventions can promote reverse remodelling at structural and molecular levels. This study seeks to identify a metric of left ventricular (LV) performance that reflects the degree of my...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
June 2026
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| In: |
ESC heart failure
Year: 2026, Volume: 13, Issue: 3, Pages: 1-15 |
| ISSN: | 2055-5822 |
| DOI: | 10.1093/eschf/xvag112 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1093/eschf/xvag112
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| Author Notes: | Balint Andras Barta, Sylvia Spiesshofer, Mihaly Ruppert, Niko Pinter, Eva Brombacher, Clemens Kreutz, Sevil Korkmaz-Icoz, Attila Olah, Alex Ali Sayour, Gabor Szabo, Bela Merkely, Tamas Radovits, and Oliver Schilling |
| Summary: | Introduction Pressure overload (PO) induces adverse myocardial remodelling, whereas efficient pressure unloading interventions can promote reverse remodelling at structural and molecular levels. This study seeks to identify a metric of left ventricular (LV) performance that reflects the degree of myocardial remodelling and reverse remodelling. Methods Male and female rats underwent surgical aortic constriction/banding (AB) to generate PO and subsequent debanding (DB) to induce pressure unloading. The architecture and function of the left ventricle were evaluated using echocardiography and pressure-volume analysis. Exploratory proteome profiling via LC-MS/MS on left ventricular samples was followed by Least Absolute Shrinkage and Selection Operator-based feature selection on existing data to determine LV parameters linked to myocardial proteomic changes. Results Tau (tau), the time constant of LV isovolumic pressure decay and an index of active relaxation, and LV mass showed the strongest associations with proteome-wide abundance changes. With 842 associated proteins and 154 overrepresented gene ontology terms, Tau demonstrated a strong correlation with LV proteomic changes during myocardial remodelling, and reverse remodelling. Nineteen Tau-associated proteins had an AUC > 0.85 when discriminating remodelled proteomes of AB rats from non-banded counterparts. Network analysis reveals varied protein-protein correlations across circumstances and indicates transcription factors regulating Tau-associated proteome changes. Across sham (Co), 6- and 12-week banding (AB6/AB12), and debanding after 6 weeks followed by 6 weeks unloading (DB), tau showed the largest set of associated proteins (n = 842) and enriched processes. Conclusion Left ventricular active relaxation, quantified by Tau, most comprehensively reflects myocardial proteomic remodelling during pressure overload and unloading. Indices of diastolic relaxation may therefore represent integrative functional readouts of molecular remodelling and potential translational markers of reverse remodelling. |
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| Item Description: | Veröffentlicht: 17 April 2026 Gesehen am 14.09.2026 |
| Physical Description: | Online Resource |
| ISSN: | 2055-5822 |
| DOI: | 10.1093/eschf/xvag112 |