Defective autophagy in vascular smooth muscle cells accelerates senescence and promotes XXXX formation and @entity731 .

@entity455 @entity30527 @entity10182 @entity71274 @entity19 @entity641 @entity1235 @entity995 @entity19149 @entity731 @entity850 @entity42066 @entity65 @entity3842 @entity8233
UNASSIGNED: Autophagy is triggered in vascular smooth muscle cells (VSMCs) of diseased arterial vessels. However, the role of VSMC autophagy in @entity65 is poorly understood. Therefore, we investigated the effect of defective autophagy on VSMC survival and phenotype and its significance in the development of @entity8233 and @entity731 . Tissue-specific deletion of the essential autophagy gene @entity30527 in @entity19 VSMCs ( @entity30527 (-/-) VSMCs) caused accumulation of @entity42066 / @entity42066 and accelerated the development of stress-induced premature senescence as shown by cellular and nuclear hypertrophy, @entity3842 -RB-mediated G1 proliferative arrest and senescence-associated @entity71274 activity. Transfection of @entity42066 -encoding plasmid DNA in @entity30527 (+/+) VSMCs induced similar features, suggesting that accumulation of @entity42066 promotes VSMC senescence. Interestingly, @entity30527 (-/-) VSMCs were resistant to oxidative stress-induced cell death as compared to controls. This effect was attributed to nuclear translocation of the transcription factor @entity10182 resulting in upregulation of several antioxidative enzymes. In vivo, defective VSMC autophagy led to upregulation of @entity1235 , @entity641 and @entity19149 and promoted @entity8233 and diet-induced @entity731 . Lesions of VSMC-specific @entity30527 knockout @entity19 were characterized by increased total collagen deposition, nuclear hypertrophy, @entity3842 upregulation, @entity995 , and @entity71274 activity, all features typical of cellular senescence. To conclude, autophagy is crucial for VSMC function, phenotype, and survival. Defective autophagy in VSMCs accelerates senescence and promotes ligation-induced @entity8233 formation and diet-induced @entity731 , implying that autophagy inhibition as therapeutic strategy in the treatment of neointimal @entity850 and @entity731 would be unfavorable. Conversely, stimulation of autophagy could be a valuable new strategy in the treatment of @entity455 .
