A defect in endothelial autophagy occurs in patients with nonalcoholic steatohepatitis and promotes inflammation and fibrosis

Autophagy is a physiological process controlling endothelial homeostasis in vascular beds outside the liver. This study demonstrates that autophagy is defective in liver endothelial cells of patients with NASH and that this defect promotes liver inflammation and fibrosis at early stages of NASH, but also at advanced stages of chronic liver disease. We used transcriptomic analysis to evaluate the global effect of autophagy deficiency in liver sinusoidal endothelial cells' (LSECs) gene expression LSECs were isolated from Atg5lox/lox and Atg5lox/lox;VE-cadherin-Cre mice fed a high fat diet for 2 weeks. RNA were extracted in TRIzol reagent. Microarray based whole transcriptome analysis was conducted, and Mouse ClariomS arrays were hybridized. Genes were considered significantly regulated when fold-change was ≥1.5 and uncorrected p-value ≤0.05. Hierarchical clustering was performed using hclust (R) with Euclidean distance and Ward agglomeration method.