2. Academic Validation
  3. Soluble neprilysin is associated with myocardial damage and systolic dysfunction in an animal model of doxorubicin-induced cardiotoxicity

Soluble neprilysin is associated with myocardial damage and systolic dysfunction in an animal model of doxorubicin-induced cardiotoxicity

  • Cardiooncology. 2026 Jan 8;12(1):3. doi: 10.1186/s40959-025-00397-4.
Aleksandra M Sobiborowicz-Sadowska 1,  Katarzyna Kamińska 2,  Dorota Sztechman 2,  Katarzyna Matusik 3,  Łukasz Koperski 4,  Karol Borensztejn 5,  Agnieszka Cudnoch-Jędrzejewska 2
Affiliations

Affiliations

  • 1 Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1b, Warsaw, 02-097, Poland. [email protected].
  • 2 Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1b, Warsaw, 02-097, Poland.
  • 3 Doctoral School, Medical University of Warsaw, Warsaw, 02-091, Poland.
  • 4 Chair and Department of Pathology, Medical University of Warsaw, Pawińskiego 3B, Warsaw, 02-004, Poland.
  • 5 Faculty of Medicine, Medical University of Warsaw, Banacha 1b, Warsaw, 02-097, Poland.
PMID: 41508006 DOI: 10.1186/s40959-025-00397-4
Abstract

Introduction: Anthracycline-induced cardiotoxicity (AIC) is a serious complication of chemotherapy, and there is a need for cost-effective biomarkers to enable risk stratification. Serum Neprilysin (sNEP) has been investigated as a biomarker in various cardiovascular conditions, but its role in AIC has not been evaluated.

Methods: Twelve-week-old Sprague-Dawley rats received intraperitoneal doxorubicin (DOX) either as a single 20 mg/kg dose (acute model, n = 8), four weekly doses of 5 mg/kg (chronic model, n = 11), or saline (controls, n = 8 for each model). Echocardiography was performed at baseline and on the final study day. Blood and left ventricular (LV) tissue were collected within 24 h (acute model) or one week (chronic model) after the last injection. NEP protein and mRNA expression were measured in LV tissue, and sNEP concentrations were determined in serum.

Results: In the chronic AIC model, LV NEP protein expression was significantly reduced compared with controls (982.56 ± 90.57 vs. 1132.86 ± 132.30 ng/L, p < 0.05). In the acute model, sNEP levels showed a strong positive correlation with the severity of LV cardiomyocyte vacuolization (rs = 0.81, p < 0.05). In the chronic model, sNEP levels were strongly and negatively correlated with cardiac output (r = - 0.91, p < 0.05).

Conclusions: Chronic DOX exposure reduces LV NEP protein expression. Elevated serum sNEP is associated with greater early cardiomyocyte injury, while in chronic AIC, it correlates with a more severe decline in cardiac output. These findings suggest sNEP may be a potential biomarker for AIC.

Keywords

Cardiotoxicity; Doxorubicin; Echocardiography; Histopathology; Neprilysin.

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