Figure 3.

Potential mechanism by which macrophage ER stress GSK3α signaling promotes atherosclerosis. Multiple cardiovascular risk factors promote ER stress which leads to the activation of the adaptive UPR. PERK signaling can increase GSK3α/β activity. Evidence from our lab suggests that signaling through GSK3α can promote macrophage foam cell formation, activate inflammatory cytokine production and enhance CHOP expression leading to apoptosis. In support of this model, we have shown that GSK3α-deficiency in macrophages is associated with attenuated atherosclerosis.