Acute liver failure is associated with significant mortality. However, the underlying pathophysiological mechanism is not yet fully understood. Suppressor of cytokine signaling-1 (SOCS1), which is a negative-feedback molecule for cytokine signaling, has been shown to be rapidly induced during liver injury. Here, using liver-specific SOCS1-conditional-knockout mice, we demonstrated that SOCS1 deletion in hepatocytes enhanced concanavalin A (

Endothelial dysfunction is thought to play an important role for the development of atherosclerosis. Autophagy is the mechanism by which organelles, aggregated protein, and even lipid droplet are broken down. Since hyperlipidemia can cause endothelial cell dysfunction during the early stage of atherosclerosis, there may be link between atherosclerosis and endothelial autophagy. To address this issue, we generated endothelial specific Atg7 knockout in apoE deficient mice (Atg7 endo /apoE). En face analysis of Oil-red O stained whole aorta showed Atg7 endo /apoE double knockout mice had severe atherosclerosis. At 16 week old, apoE single knockout mice (apoE) had 9.7 % of oil-red O positive area while Atg7 endo /apoE mice had 18.6 % (n=10, 9 mice per group). The composition of macrophages, collagen, and lipid in atherosclerotic lesions were similar between control and Atg7 endo /apoE mice. Body weight and fat composition were also similar between the two groups, as were blood glucose, triglyceride, cholesterol, and fatty acid levels. At 24 weeks of age, en face analysis of aorta showed even more disparity in lesion size between control and Atg7 endo /apoE mice (apoE mice, 15.4%, Atg7 endo /apoE mice, 36.2%, n=10, 7 mice per group). Secretion of various chemokine, such as MCP-1 from Atg7 knockdown human umbilical vein endothelial cell (shATG7 HUVECs) was 10-fold higher that of control cells. These results suggest that autophagy deficiency in endothelial cells accelerate in vivo atherosclerosis. This augmentation may result from an enhanced inflammatory response.

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