The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Enhanced Efferocytosis of Apoptotic Cardiomyocytes Through Myeloid-Epithelial-Reproductive Tyrosine Kinase Links Acute Inflammation Resolution to Cardiac Repair After Infarction
Open accessAbstract
Rationale: Efficient clearance of apoptotic cells (efferocytosis) is a prerequisite for inflammation resolution and tissue repair. After myocardial infarction, phagocytes are recruited to the heart and promote clearance of dying cardiomyocytes. The molecular mechanisms of efferocytosis of cardiomyocytes and in the myocardium are unknown. The injured heart provides a unique model to examine relationships between efferocytosis and subsequent inflammation resolution, tissue remodeling, and organ function. Objective: We set out to identify mechanisms of dying cardiomyocyte engulfment by phagocytes and, for the first time, to assess the causal significance of disrupting efferocytosis during myocardial infarction. Methods and Results: In contrast to other apoptotic cell receptors, macrophage myeloid-epithelial-reproductive tyrosine kinase was necessary and sufficient for efferocytosis of cardiomyocytes ex vivo. In mice, Mertk was specifically induced in Ly6c LO myocardial phagocytes after experimental coronary occlusion. Mertk deficiency led to an accumulation of apoptotic cardiomyocytes, independently of changes in noncardiomyocytes, and a reduced index of in vivo efferocytosis. Importantly, suppressed efferocytosis preceded increases in myocardial infarct size and led to delayed inflammation resolution and reduced systolic performance. Reduced cardiac function was reproduced in chimeric mice deficient in bone marrow Mertk ; reciprocal transplantation of Mertk +/+ marrow into Mertk −/− mice corrected systolic dysfunction. Interestingly, an inactivated form of myeloid-epithelial-reproductive tyrosine kinase, known as solMER, was identified in infarcted myocardium, implicating a natural mechanism of myeloid-epithelial-reproductive tyrosine kinase inactivation after myocardial infarction. Conclusions: These data collectively and directly link efferocytosis to wound healing in the heart and identify Mertk as a significant link between acute inflammation resolution and organ function.
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Cites
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Phagocytosis and clearance of apoptotic cells is mediated by MER
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Cited by
The inflammatory response in myocardial injury, repair, and remodelling
Frangogiannis, N. G. (2014) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2014.28 · Cited by 1,738
Efferocytosis in health and disease
Doran, A. C., Yurdagul, A., & Tabas, I. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0240-6 · Cited by 1,066
Self-Renewing Resident Cardiac Macrophages Limit Adverse Remodeling Following Myocardial Infarction
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Cardioimmunology: the immune system in cardiac homeostasis and disease
Swirski, F. K., & Nahrendorf, M. (2018) · Nature Reviews Immunology · doi:10.1038/s41577-018-0065-8 · Cited by 849
A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart
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Metadata
- Authors
- Wan, E., Yeap, X. Y., Dehn, S., Terry, R., Novak, M., Zhang, S., Iwata, S., Han, X., Homma, S., Drosatos, K., Lomasney, J., Engman, D. M., Miller, S. D., Vaughan, D. E., Morrow, J. P., Kishore, R., & Thorp, E. B.
- Venue
- Circulation Research
- Published
- 2013-09-27
- Volume
- 113
- Issue
- 8
- Pages
- 1004-1012
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2111035891
- Cited by
- 383
- References
- 16
- FWCI
- 7.39
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Enhanced Efferocytosis of Apoptotic Cardiomyocytes Through Myeloid-Epithelial-Reproductive Tyrosine Kinase Links Acute Inflammation Resolution to Cardiac Repair After Infarction. https://app.cochat.ai/papers/10.1161/circresaha.113.301198
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- Wan, E., Yeap, X. Y., Dehn, S., Terry, R., Novak, M., Zhang, S., Iwata, S., Han, X., Homma, S., Drosatos, K., Lomasney, J., Engman, D. M., Miller, S. D., Vaughan, D. E., Morrow, J. P., Kishore, R., & Thorp, E. B. (2013). Enhanced Efferocytosis of Apoptotic Cardiomyocytes Through Myeloid-Epithelial-Reproductive Tyrosine Kinase Links Acute Inflammation Resolution to Cardiac Repair After Infarction. Circulation Research. https://doi.org/10.1161/circresaha.113.301198
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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