Aloe-emodin derivative produces anti-atherosclerosis effect by reinforcing AMBRA1-mediated endothelial autophagy

Atherosclerosis is an inflammatory disease of high lethality associated with endothelial dysfunction. Due to the pathophysiological complexity and our incomplete understanding of the mechanisms for the development and progression of atherosclerosis, effective means for the prevention and treatment of atherosclerosis still need further exploration. This study was designed to investigate the potential effects and underlying mechanisms of aloe-emodin derivative (AED) on atherosclerosis. High fat diet (HFD) treated ApoE-/- mice were used as an animal model of atherosclerosis. Intragastric administration of aloe-emodin (AE) or AED for 12 weeks markedly reduced the atherosclerotic plaque in aorta with decreased plaque area, lipid accumulation, macrophage infiltration, collagen content and metabolic abnormalities. By comparison, AED produced more potent anti-atherosclerosis effects than AE at the same dose. AED enhanced production of autophagy flux in cultured human aortic endothelial cells (HAECs). Moreover, AED increased the expression of activating molecule in Beclin1-regulated autophagy 1 (AMBRA1), a key protein involved in autophagosome formation. Furthermore, knockdown of AMBRA1 blocked the promotion effect of AED on autophagy in HAECs. Taken together, AED facilitates endothelial autophagy via AMBRA1 during the progression of atherosclerosis, suggesting the potential application of this compound for atherosclerosis treatment.