Endothelial autophagic flux hampers atherosclerotic lesion development

Abstract

Blood flowing in arteries generates shear forces at the surface of the vascular endothelium that control its anti-atherogenic properties. However, due to the architecture of the vascular tree, these shear forces are heterogeneous and atherosclerotic plaques develop preferentially in areas where shear is low or disturbed. Here we review our recent study showing that elevated shear forces stimulate endothelial autophagic flux and that inactivating the endothelial macroautophagy/autophagy pathway promotes a proinflammatory, prosenescent and proapoptotic cell phenotype despite the presence of atheroprotective shear forces. Specific deficiency in endothelial autophagy in a murine model of atherosclerosis stimulates the development of atherosclerotic lesions exclusively in areas of the vasculature that are normally resistant to atherosclerosis. Our findings demonstrate that adequate endothelial autophagic flux limits atherosclerotic plaque formation by preventing endothelial apoptosis, senescence and inflammation.

Sex-dependent differences in the secretome of human endothelial cells

“…Speci cally, female cells appear more prone to autophagy, and our preliminary results in serum-deprived female ECs support this hypothesis (Cattaneo et al, manuscript in preparation). Since a protective role against atherosclerosis has been suggested for autophagy [67], it will be of great interest to study whether this mechanism might represent the path chosen by female ECs to contrast endothelial injures and in ammation.…”

Autophagy in endothelial cells and tumor angiogenesis

“…Mounting evidence shows that autophagy has a vital role in atherosclerogenesis. In a murine atherosclerotic model, genetic inactivation of EC autophagy increases plaque burden exclusively in high shear stress areas that are normally resistant to atherosclerotic plaque formation [27, 46]. This indicates that autophagy is essential for atheroprotection by restoring endothelial vascular wear and tear under physiological blood flow.…”

Downregulation of LncRNA NORAD promotes Ox-LDL-induced vascular endothelial cell injury and atherosclerosis

“…In addition to apoptosis, vascular endothelial cell senescence occurs in atherosclerotic arteries and may be an important initial cellular change in atherosclerosis progression [33]. Vascular endothelial cell senescence is detected with two main methods: β-galactosidase staining and cell cycle assay.…”