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Cardiac Immune Cell–Mediated Inflammatory Responses Exacerbate Myocardial Cell Injury in Mice

Daniel R. Whitfield, PhD1, Emily J. Morrison, PhD, Thomas L. Harrington, PhD, Sarah K. Donnelly, MD, PhD ORCID *

1 Department of Cardiology and Molecular Medicine, Monash University, Melbourne, VIC, Australia

DOI: 10.18081/2378-5225/14.140  
Cited by 0

 Article history: Received 30 August 2025 · Revised 12 September 2025 · Accepted 22 October 2025 · Published 09 November 2025

© 2025 Donnelly, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0). 

CC BY 4.0                                                                                                   

Abstract

Background: Myocardial cell injury is a central event in the pathogenesis of acute and chronic cardiac diseases and is strongly influenced by inflammatory responses within the injured myocardium. Macrophages are among the earliest and most abundant immune cells recruited to the heart following injury; however, their precise contribution to cardiomyocyte damage remains incompletely defined.

Methods: Myocardial injury was induced in adult C57BL/6J mice, and inflammatory responses were assessed at defined time points. Macrophage infiltration and phenotype were evaluated using immunohistochemistry and flow cytometry. Systemic macrophage depletion was achieved using clodronate liposomes to determine the contribution of macrophages to myocardial injury. Cardiomyocyte injury and tissue damage were quantified histologically, and myocardial expression of pro-inflammatory cytokines was assessed by immunohistochemical analysis.

Results: Myocardial injury resulted in robust macrophage accumulation within the heart, with a predominance of inflammatory Ly6C^high macrophage subsets during the acute injury phase. Increased macrophage infiltration closely correlated with enhanced cardiomyocyte injury and elevated myocardial expression of TNF-α and IL-1β. Macrophage depletion significantly reduced cardiac macrophage numbers, attenuated pro-inflammatory cytokine expression, and led to a marked reduction in myocardial cell injury and tissue damage. These findings demonstrate a direct association between macrophage-driven inflammation and cardiomyocyte injury severity.

Conclusions: Macrophage-driven inflammatory responses play a critical role in amplifying myocardial cell injury in experimental mouse models. Targeted modulation of macrophage recruitment and inflammatory signaling may represent a promising therapeutic strategy to limit inflammation-induced myocardial damage and improve cardiac outcomes following injury.

Keywords: Myocardial cell injury; Cardiac inflammation; Macrophages; Macrophage polarization; Pro-inflammatory cytokines

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BM-Publisher · Pathophysiology of Cell Injury Journal (PCIJ) · E-ISSN 2378-5225 · DOI Prefix 10.18081/pcij/2378-5225

Pathophysiology of Cell Injury Journal (PCIJ)
E-ISSN 2378-5225 · Biannual
BM-Publisher (London, UK)
Open Access

Vol 14, Issue 2 (November 2025), pp. 140–162

How to cite (AMA)

Whitfield DR, Morrison MJ, Harrington TL, Donnelly SK. Cardiac Immune Cell–Mediated Inflammatory Responses Exacerbate Myocardial Cell Injury in Mice. Pathophysiology of Cell Injury Journal (PCIJ). 2025;14(2):140–162. doi: 10.18081/2378-5225/14.140.

More citation

Daniel R. Whitfield, E. J. M. T. L. H. S. K. D. (2025). . Pathophysiology of Cell Injury Journal (PCIJ), . https://pcij.net/archives/2184
Daniel R. Whitfield, Emily J. Morrison, Thomas L. Harrington, Sarah K. Donnelly. \".\" Pathophysiology of Cell Injury Journal (PCIJ), 2025, pp. . https://pcij.net/archives/2184
Daniel R. Whitfield, Emily J. Morrison, Thomas L. Harrington, Sarah K. Donnelly. . Pathophysiology of Cell Injury Journal (PCIJ). 2025;:. https://pcij.net/archives/2184
Daniel R. Whitfield, Emily J. Morrison, Thomas L. Harrington, Sarah K. Donnelly (2025) . Pathophysiology of Cell Injury Journal (PCIJ), , pp. . Available at: https://pcij.net/archives/2184
@article{daniel-r-whitfield-emily-j-morrison-thomas-l-harrington-sarah-k-donnelly-2025, title = {}, author = {Daniel R. Whitfield, Emily J. Morrison, Thomas L. Harrington, Sarah K. Donnelly}, journal = {Pathophysiology of Cell Injury Journal (PCIJ)}, year = {2025}, url = {https://pcij.net/archives/2184}, }
TY - JOUR AU - Daniel R. Whitfield, Emily J. Morrison, Thomas L. Harrington, Sarah K. Donnelly TI - JO - Pathophysiology of Cell Injury Journal (PCIJ) PY - 2025 UR - https://pcij.net/archives/2184 ER -

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