Macrophage depletion impairs wound healing and increases left ventricular remodeling after myocardial injury in mice
| Autor: | Marja J. A. van Luyn, Nico van Rooijen, Martin C. Harmsen, Machteld J. van Amerongen, Arjen H. Petersen |
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| Přispěvatelé: | Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Vascular Ageing Programme (VAP) |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A MECHANISM Pathology medicine.medical_specialty GROWTH-FACTOR medicine.medical_treatment Neovascularization Physiologic Pathology and Forensic Medicine Neovascularization Transforming Growth Factor beta1 Mice TENASCIN-C medicine Animals Myocardial infarction STIMULATING FACTOR TREATMENT Ventricular remodeling IN-VIVO REPAIR Wound Healing Ventricular Remodeling business.industry Growth factor Macrophages Myocardium INFLAMMATORY RESPONSE Granulation tissue medicine.disease Coronary Vessels Mice Inbred C57BL Vascular endothelial growth factor A LATE REPERFUSION medicine.anatomical_structure Heart Injuries Immunology medicine.symptom business Wound healing INFARCTION Myofibroblast MYOFIBROBLASTS Regular Articles |
| Zdroj: | American Journal of Pathology, 170(3), 818-829. ELSEVIER SCIENCE INC |
| ISSN: | 0002-9440 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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