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Introduction <p>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.</p> Methods <p>Twelve-week-old Sprague–Dawley rats received intraperitoneal doxorubicin (DOX) either as a single 20&#xa0;mg/kg dose (acute model, <i>n</i> = 8), four weekly doses of 5&#xa0;mg/kg (chronic model, <i>n</i> = 11), or saline (controls, <i>n</i> = 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&#xa0;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.</p> Results <p>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, <i>p</i> &lt; 0.05). In the acute model, sNEP levels showed a strong positive correlation with the severity of LV cardiomyocyte vacuolization (<i>r</i>s = 0.81, <i>p</i> &lt; 0.05). In the chronic model, sNEP levels were strongly and negatively correlated with cardiac output (<i>r</i> = − 0.91, <i>p</i> &lt; 0.05).</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月8日

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  • Aleksandra M. Sobiborowicz-Sadowska,
  • Katarzyna Kamińska,
  • Dorota Sztechman,
  • Katarzyna Matusik,
  • Łukasz Koperski,
  • Karol Borensztejn,
  • Agnieszka Cudnoch-Jędrzejewska

摘要

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.