Role of macrophages in regression of atherosclerosis

The exact role of macrophages in regression is still not clear. It appears that some of their functions are beneficial, while others are detrimental. Among their beneficial functions are: (1) their ability to phagocytize cellular and extracellular debris and remove them outside the arterial wall. This function may be enhanced by the macrophage's own secretion of fibronectin; (2) their ability to solubilize necrotic debris by their complement of hydrolytic enzymes, thus, rendering them diffusible through the arterial wall; and, (3) their secretion of SMC mitogen and components of the arterial wall. Our work supports the role of macrophages in the removal of necrotic debris by the mechanisms cited in (1) and (2) above. On the other hand, macrophages may be detrimental to regression if they secrete an excess of the same hydrolytic enzymes, mentioned above as being beneficial, and if directed towards normal arterial wall components. This can result in disorganization and degradation of these components, and in more necrosis, as was seen at the six-week regression period in our sequential study. Cell debris resulting from necrosis of SMC and from death of macrophages themselves may form nidi for calcific bodies to occur. Our work suggests this may be the case during regression. Finally, excess stimulation of SMC, mitogen, and the secretion of the arterial wall components may contribute to the lesion growth and could explain the lack of regression in some species and under certain conditions. In conclusion, our hypothesis that the macrophage is a "friend" during regression appears to be only partially true, and their presence at this phase of the disease may be a "two-edged sword." On one hand, they may help in the removal of necrosis, while on the other hand, they may accelerate calcification.