Myocardial fibrosis is one of the main structural changes following cardiomyocyte injury such as infarction. Macrophages play a central role in the development of fibrotic lesions. In myocardial fibrosis, three different populations of macrophages are recognized: exudate macrophages, resident macrophages, and interstitial dendritic cells. Exudate macrophages, which are derived from blood monocytes and recruited into injured areas through chemoattractants and cell adhesion molecules, release various fibrogenic growth factors in early stages of the fibrosis. Transforming growth factor-beta and platelet-derived growth factors are proposed as the most probable growth factors produced by exudate macrophages to induce the modulation of fibroblasts towards myofibroblasts. Emerging evidence shows that macrophage-secreted nerve growth factor may also be involved in that process. The myofibroblasts are capable of producing extracellular matrix proteins which contribute to myocardial fibrosis. The exudate macrophages also participate in the induction ofapoptosis in injured myocytes and myofibroblasts in the fibrotic lesions. These apoptotic cells are phagocytized by exudate macrophages, and the macrophages themselves also disappear by apoptosis. The decrease in cellularity by apoptosis leads to the evolution of fibrous granulation tissues into scar tissues (reparative fibrosis). The resident macrophages particiapte exclusively in the late stages of the myocardial fibrosis, when their mitotic activity increases in the lesions; they are presumed to have the same roles as the exudate macrophages. In addition, the resident macrophages and interstitial dendritic cells both act as immune mediators to recruit T-lymphocytes into the lesions. In contrast to hepatic, pulmonary, and renal fibrosis, the roles of macrophage populations in myocardial fibrosis has not yet been extensively investigated.
Biomedical Reviews 1999; 10: 89-105.
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