Recruitment of monocytes into atherosclerotic plaque has been shown to drive disease progression, and the presence of a higher number of macrophages has been associated with increased plaque vulnerability. Conversely, a reduction in plaque macrophage content has been associated with plaque stabilisation; however, it has not previously been described exactly how macrophages are removed from plaques, for example in the context of statin therapy.
Potteaux et al. aimed to elucidate this mechanism by use of the mouse Apoe-/- model, which has high levels of cholesterol and therefore spontaneously develops atherosclerotic lesions. However, in this case the authors re-introduced the apoE gene (by means of an adenoviral vector), and studied what happened to the mice’s atherosclerotic plaques subsequently.
Within two days of apoE complementation, plasma cholesterol levels had returned to normal levels, and HDL cholesterol levels had increased four fold, leading to a stabilisation of plaque area. At four weeks, plaque macrophage content was noted to be 72% lower, however no egress of macrophages from plaque was noted. Rather, the authors noted that decreased monocyte recruitment, coupled with apoptosis of existing cells, led to the reduction in plaque macrophages.
In this mouse model, plaque stabilisation was seen to occur as a result of a decrease in monocyte recruitment, rather than an increase in macrophage egress. Therapies to inhibit monocyte recruitment may therefore be beneficial in stabilising plaque.
- Potteaux S, Gautier EL, Hutchison SB et al. Suppressed monocyte recruitment drives macrophage removal from atherosclerotic plaques of Apoe-/- mice during disease regression. JCI doi:10.1172/JCI43802.