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Cardiac myofibroblast engulfment of dead cells facilitates
recovery after myocardial infarction.

2Nakaya M, Watari K, Tajima M, Nakaya T, Matsuda S, Ohara H, Nishihara H, Yamaguchi H, Hashimoto
A, Nishida M, Nagasaka A, Horii Y, Ono H, Iribe G, Inoue R, Tsuda M, Inoue K, Tanaka A, Kuroda M,Nagata S, Kurose H
J Clin Invest. 2016 Dec 05

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Recommendations:
20 Dec 2016

Very GoodGiulio Gabbiani
F1000 Physiology
University of Geneva, CMU, Geneva 4,Switzerland.

INTERESTING HYPOTHESIS | NEW FINDING

DOI: 10.3410/f.727072457.793526329
This article investigates an hitherto unexplored myofibroblast function, i.e. the capacity of cardiac myofibroblasts to engulf dead myocardial cells after an infarction. The authors
elegantly show that after experimental myocardial infarct a subpopulation of myofibroblasts (derived from resident fibroblasts and from cells undergoing endothelial-mesenchymaltransition) produce milk fat globule-epidermal growth factor 8 (MFG-E8) through the transforming growth factor (TGF)-beta/serum response factor pathway. MFG-E8 in turn reduces
inflammation and favorizes dead cell engulfment as well as fibrosis and healing. Experimental MFG-E8 deficiency reduces -- while administration of MFG-E8 favorizes -- recovery
after myocardial infarction. Thus, MFG-E8 represents a new candidate for the therapeutic strategy of myocardial infarction and possibly of other fibrotic situations.
DisclosuresNone declared
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ABSTRACT

Myocardial infarction (MI) results in the generation of dead cells in the infarcted area. These cells are swiftly removed by phagocytes to minimize inflammation and limit expansionof the damaged area. However, the types of cells and molecules responsible for the engulfment of dead cells in the infarcted area remain largely unknown. In this study, wedemonstrated that cardiac myofibroblasts, which execute tissue fibrosis by producing extracellular matrix proteins, efficiently engulf dead cells. Furthermore, we identified apopulation ofcardiac myofibroblasts that appears in the heart after MI in humans and mice. We found that these cardiac myofibroblasts secrete milk fat globule-epidermal growth factor 8 (MFGE8), which promotes apoptotic engulfment, and determined that serum response factor is important for MFG-E8 production in myofibroblasts. Following MFG-E8-mediatedengulfment of apoptotic cells, myofibroblasts acquired antiinflammatory properties. MFG-E8 deficiency in mice led to the accumulation of unengulfed dead cells after MI, resulting in
exacerbated inflammatory responses and a substantial decrease in survival. Moreover, MFG-E8 administration into infarcted hearts restored cardiac function and morphology.
MFG-E8-producing myofibroblasts mainly originated from resident cardiac fibroblasts and cells that underwent endothelial-mesenchymal transition in the heart. Together, our results
reveal previously unrecognized roles of myofibroblasts in regulating apoptotic engulfment and a fundamental importance of these cells in recovery from MI.
null
DOI: 10.1172/JCI83822
PMID: 27918308
Abstract courtesy of PubMed: A service of the National
Library of Medicine and the National Institutes of Health.

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F1000 Faculty Reviews are comprehensive, open access,topical reviews written by members of the prestigious F1000Faculty. These peer reviewed articles provide context on
emerging themes in biology and medicine.

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Full text | PDF | Abstract on PubMed

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