Macrophage depletion impairs wound healing and increases left ventricular remodeling after myocardial injury in mice
Open accessAbstract
Macrophages have been suggested to be beneficial for myocardial wound healing. We investigated the role of macrophages in myocardial wound healing by inhibition of macrophage infiltration after myocardial injury. We used a murine cryoinjury model to induce left ventricular damage. Infiltrating macrophages were depleted during the 1st week after cryoinjury by serial intravenous injections of clodronate-containing liposomes. After injury, the presence of macrophages, which secreted high levels of transforming growth factor-beta and vascular endothelial growth factor-A, led to rapid removal of cell debris and replacement by granulation tissue containing inflammatory cells and blood vessels, followed by myofibroblast infiltration and collagen deposition. In macrophage-depleted hearts, nonresorbed cell debris was still observed 4 weeks after injury. Secretion of transforming growth factor-beta and vascular endothelial growth factor-A as well as neovascularization, myofibroblast infiltration, and collagen deposition decreased. Moreover, macrophage depletion resulted in a high mortality rate accompanied by increased left ventricular dilatation and wall thinning. In conclusion, infiltrating macrophage depletion markedly impairs wound healing and increases remodeling and mortality after myocardial injury, identifying the macrophage as a key player in myocardial wound healing. Based on these findings, we propose that increasing macrophage numbers early after myocardial infarction could be a clinically relevant option to promote myocardial wound healing and subsequently to reduce remodeling and heart failure.
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Accumulating evidence indicates that macrophages are critical orchestrators in healing of many tissues, including skin.
“Accumulating evidence indicates that Mp are critical orchestrators in healing of many tissues, including skin (3,4,7,48).”
From Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice (2014) · cites this paper as [48]
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- Authors
- van Amerongen, M. J., Harmsen, M. C., van Rooijen, N., Petersen, A. H., & van Luyn, M. J. A.
- Affiliations
- University Medical Center Groningen (NL)
- ORCID
- Harmsen, Martin C.
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 170
- Issue
- 3
- Pages
- 818-829
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1864893
- OpenAlex
- W2037994205
- Cited by
- 544
- References
- 37
- Citations by year
- 2026: 17 · 2025: 16 · 2024: 24 · 2023: 29 · 2022: 25 · 2021: 42 · 2020: 40 · 2019: 40 · 2018: 41 · 2017: 46 · 2016: 32 · 2015: 34 · 2014: 31 · 2013: 29 · 2012: 27
- FWCI
- 13.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- macrophages, left ventricular remodeling, myocardial injury, macrophage depletion, clodronate liposomes, TGF-beta, VEGF-A, collagen deposition, neovascularization, heart failure, mortality
- MeSH terms
- Animals, Coronary Vessels, Heart Injuries, Macrophages, Male, Mice, Inbred C57BL, Myocardium, Wound Healing, Neovascularization, Physiologic, Ventricular Remodeling, Vascular Endothelial Growth Factor A, Mice, Transforming Growth Factor beta1
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