Figure 7.

Schematic summarizing findings of Cer16 effect on human LMVECs isolated from nonsmokers compared with those isolated from smokers. Human naive LMVECs respond to ceramide by increasing ER stress and mitochondrial depolarization, which is associated with AIF-mediated, caspase-independent (Akt-inhibited caspases) apoptosis and autophagy (top). Chronic exposure to cigarette smoke (CS) is associated with Akt hyperphosphorylation and increased levels of SPH, which contributes to robust induction of autophagy associated with high HMGB1 levels, and which, together, contribute to develop an apoptotic-resistant phenotype (bottom).