In vivo responses of macrophages and myofibroblasts in the healing following isoproterenol-induced myocardial injury in rats

To clarify the relation between macrophage and myofibroblast involvement in various myocardial diseases, the authors investigated the kinetics of these cells in the healing (scar tissue formation) following isoproterenol-induced myocardial injury in rats. Alpha-smooth muscle actin (alpha-SMA) expressing myofibroblasts were seen at the border of the affected area and appeared in the greatest numbers on days 3-7 post-injection, followed by a gradual decrease by day 35. The peak on day 3 was consistent with the timing of the highest proliferative activity of myofibroblasts. The number of ED1-positive macrophages began to increase as early as day 1, reaching a peak on day 3 within the injured myocardium. The expansion of ED1-positive macrophages preceded an increased number of alpha-SMA-positive myofibroblasts suggesting that myofibroblast proliferation and activation may be mediated by factors released by ED1-positive macrophages in response to myocardial injury. The number of ED2-positive tissue-fixed, resident macrophages gradually, increased from day 3 post-injection, and peaked on day 14, but the number of ED2-positive macrophages was consistently fewer than that of ED1-positive macrophages during the 35 day-observation period after the injection. The labelling index of the ED2-positive cells was maximal on day 14, indicative of local proliferation of resident macrophages. In the healing process after myocardial injury, ED1-positive macrophages increase markedly in the early stages: ED2-positive macrophages appear later.