e22 Arterioscler Thromb Vasc Biol October 2014 marker CD68 and in keeping with our studies of rabbits they reported that early American Heart Association type II lesions had the highest frequency of macrophage proliferation. A major limitation of the study by Robbins et al is that it is difficult to extrapolate their observations to human atherosclerosis. Normal human muscular arteries have an intima (often referred to as diffuse intimal thickening) that contains resident macrophages. 18 Normal mouse arteries do not have an intima. Thus in the mouse, monocyte recruitment leads to the formation of the intima and must predominate at early stages. In the human, it may be that resident macrophages are also induced to proliferate as part of the early inflammatory response and that macrophage proliferation contributes more to expansion of early lesions in humans than it would in mice. In fact, cells in human diffuse intimal thickenings have been shown to express proliferation markers. 16 Additional unanswered questions are to what degree the macrophage proliferation actually contributes to lesion progression rather than just replenishment of the macrophage population and to what degree the scavenger receptor status regulates the proliferation. This is underscored by the controversy that exists as to whether the Msr1 plays a role in lesion development as there has been contradictory evidence that knockout or overexpression of the Msr1 affects lesion area and composition in several different mouse models. 19–25 Nevertheless, the major strength of the studies of Robbins et al is that based on several different and simultaneously used quantitative approaches, they have conclusively demonstrated that macrophage proliferation contributes to maintaining the macrophage population of mouse lesions. Furthermore, this study has refocused our attention on the importance of macrophage proliferation in atherosclerosis and has for the first time provided quantitative evidence that at certain stages of the disease, macrophage proliferation may be a predominant mechanism supporting the chronic inflammatory response that is characteristic of atherosclerosis.