Effects of global AIF1 deficiency on atherosclerosis were assessed by crossing Aif1<sup>-/-</sup> and ApoE<sup>-/-</sup> mice, and provoking hyperlipidemia with high fat diet feeding.
Concerning the presence of macrophages, subjects with arteriosclerosis had significantly more positive expression of ionized calcium-binding adapter molecule-1 (IBA-1), a marker of macrophages, than subjects without arteriosclerosis (P < 0.001).
Transgenic mice in which AIF-1 expression is driven by the G/C modified SM22 alpha promoter to restrict AIF-1 expression to VSMC develop significantly increased atherosclerosis compared with wild-type control mice when fed a high-fat diet (P=0.022).
Inhibition of NFAT signalling, by shifting the AIF-1/IRT-1 ratio, may be an attractive target to regulate the VSMC response to injury and manipulate plaque stability in atherosclerosis.