Apolipoprotein L6, Induced in Atherosclerotic Lesions, Promotes Apoptosis and Blocks Beclin 1-dependent Autophagy in Atherosclerotic Cells

摘要: Inflammatory cytokine-regulated apoptosis and autophagy play pivotal roles in plaque rupture thrombosis of atherosclerotic lesions. However, the molecular interplay between vascular cells has not been investigated. Our prior study showed that human apolipoprotein L6 (ApoL6), a pro-apoptotic BH3-only member Bcl-2 family, was one downstream targets interferon-γ (INFγ), which sensitizes lesion-derived (LDCs) to Fas-induced apoptosis. To investigate whether ApoL6 plays causal role autophagy, this study, we demonstrate IFNγ treatment itself strongly induces ApoL6, is highly expressed partially co-localized with activated caspase 3 smooth muscle In addition, overexpression promotes reactive oxygen species (ROS) generation, activation, subsequent apoptosis, can be blocked by pan inhibitor ROS scavenger. Knockdown expression siApoL6 suppresses INFγ- Fas-mediated Further, binds Bcl-XL, most abundant anti-death proteins LDCs. Interestingly, forced LDCs degradation Beclin 1, accumulation p62, attenuation LC3-II formation translocation thus whereas reverts phenotype. Taken together, our results suggest regulates both SMCs. IFNγ-initiated, ApoL6-induced may an important factor causing instability potential therapeutic target for treating atherosclerosis cardiovascular disease.