MafB promotes atherosclerosis by inhibiting foam-cell apoptosis

MafB and the role of macrophage apoptosis in atherosclerosis: A time to kill, a time to heal

“…Macrophage apoptosis is protective in early lesions and diminishes lesion progression because of efficient efferocytosis by nearby macrophages, while conversely it promotes lesion vulnerability and development of necrotic cores in advanced lesions because of defective efferocytosis. The first part of this hypothesis was corroborated by Hamada [13] by showing that MafB inhibition accelerated foam-cell apoptosis, which subsequently led to the attenuation of the early atherogenic lesion. In this issue of Atherosclerosis, Hasegawa [14] verifies the second part of this hypothesis by demonstrating that exacerbated macrophage apoptosis in advanced atherosclerosis (achieved through macrophage-specific deletion of MafB) results in more unstable and more vulnerable lesions despite similar atherosclerosis extension.…”

“…This antiapoptotic role of MafB in macrophages was subsequently confirmed [13] and the protective mechanisms revealed. MafB mediates the oxidized LDL-activated LXR/RXR-induced expression of apoptosis inhibitor of macrophages (AIM); thus in the absence of MafB, LXR/ RXR fails to activate the antiapoptotic AIM protein [13], thus boosting macrophage apoptosis.…”

“…The same group authoring this editorialized article previously discovered the antiapoptotic role of MafB in macrophages because macrophage-specific forced expression of MafB attenuated macrophage apoptosis induced by oxidative stress [21]. This antiapoptotic role of MafB in macrophages was subsequently confirmed [13] and the protective mechanisms revealed. MafB mediates the oxidized LDL-activated LXR/RXR-induced expression of apoptosis inhibitor of macrophages (AIM); thus in the absence of MafB, LXR/ RXR fails to activate the antiapoptotic AIM protein [13], thus boosting macrophage apoptosis.…”

“…On the contrary, Hamada previously demonstrated that macrophage-selective MafB inhibition in early atherosclerotic lesions triggered accelerated foam-cell apoptosis, which subsequently led to the attenuation of atherogenesis [13]. These apparently contradicting results can be reconciled under the abovementioned hypothesis, that macrophage apoptosis is protective during the early stages of atherosclerosis by reducing cellularity (the main mechanism of plaque growth in early lesions) while conversely macrophage apoptosis is deleterious in advanced atherosclerosis because it increases necrotic core and exacerbates plaque vulnerability.…”

Dimeric combinations of MafB, cFos and cJun control the apoptosis-survival balance in limb morphogenesis

“…Importantly, a recent study in mice revealed a novel function for MafB in inhibiting foam-cell apoptosis, which in turn accelerates atherogenesis (Hamada et al, 2014). By contrast, MafBdeficient mice have phenotypically normal limbs (Satoru Takahashi, personal communication).…”