Abstract
Endotrophin is a matrikine released from the C-terminus of the alpha-3 chain of type VI collagen, gaining increasing attention both as a biomarker and as a therapeutic target in the cardiometabolic space. So far, it has been quantified in circulation by the PRO-C6 assay, which detects different-sized proteolytic fragments of the C-terminus, including endotrophin. Here, we developed and evaluated a novel immunoassay targeting the full-length endotrophin, explored its biological relevance in two clinical cohorts of HFpEF, and investigated its potential as a prognostic biomarker. Increased circulating Endotrophin levels were associated with cardiovascular and all-cause mortality in both cohorts. When adjusting for relevant confounders, Endotrophin remained independently associated with both endpoints only in cohort 1. This work emphasizes the importance of the extracellular matrix in disease, confirms the prognostic value of endotrophin, and provides a novel tool for further exploration of its biological role.
Data availability
The data generated and analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- ECM:
-
Extracellular matrix
- HF:
-
Heart failure
- HFpEF:
-
Heart failure with preserved ejection fraction
- HFrEF:
-
Heart failure with reduced ejection fraction
- ELISA:
-
Enzyme-linked immunosorbent assay
- LOB:
-
Limit of blank
- LLOQ:
-
Lower limit of quantification
- ULOQ:
-
Upper limit of quantification
- LVEF:
-
Left ventricular ejection fraction
- eGFR:
-
Estimated glomerular filtration rate
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Funding
The present work was supported by the Danish Research Foundation (“Den danske forskningsfond”) to EA. EA was partly funded by Nordic Bioscience A/S as a PhD candidate at the time of research.
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EA developed the methodology, performed the experiments and the data analysis, and wrote the first draft. ER and BL handled the clinical samples and the clinical data. MC performed the adaptation of the methodology for the automated platform and wrote the relevant section of the manuscript. SS and MK provided scientific guidance and supervision. FG participated in the conceptualization, supervision, and interpretation of the results. AG and ABG provided the clinical samples and participated in the interpretation of the results. All authors reviewed the manuscript.
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EA, MC, SS, FG, and MK are shareholders and employees at Nordic Bioscience A/S at the time of publication. The rest of the authors have no conflict of interest to report concerning this manuscript. The authors declare a potential conflict of interest due to EA, FG, and MK being inventors on a patent application regarding the endotrophin technology described in this manuscript. The patent application is pending to Nordic Bioscience A/S.
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Angeli, E., Revuelta-López, E., López, B. et al. Characterization of a novel assay for full-length endotrophin in heart failure with preserved ejection fraction. Sci Rep (2026). https://doi.org/10.1038/s41598-026-40557-9
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DOI: https://doi.org/10.1038/s41598-026-40557-9
