Autophagy protein 5 controls flow-dependent endothelial functions

Abstract

Dysregulated autophagy is associated with cardiovascular and metabolic diseases, where impaired flow-mediated endothelial cell responses promote cardiovascular risk. The mechanism by which the autophagy machinery regulates endothelial functions is complex. We applied multi-omics approaches and in vitro and in vivo functional assays to decipher the diverse roles of autophagy in endothelial cells. We demonstrate that autophagy regulates VEGF-dependent VEGFR signaling and VEGFR-mediated and flow-mediated eNOS activation. Endothelial ATG5 deficiency in vivo results in selective loss of flow-induced vasodilation in mesenteric arteries and kidneys and increased cerebral and renal vascular resistance in vivo. We found a crucial pathophysiological role for autophagy in endothelial cells in flow-mediated outward arterial remodeling, prevention of neointima formation following wire injury, and recovery after myocardial infarction. Together, these findings unravel a fundamental role of autophagy in endothelial function, linking cell proteostasis to mechanosensing.

Autophagy degrades immunogenic endogenous retroelements induced by 5-azacytidine in acute myeloid leukemia

“…This indicates that, at the time of diagnosis, AML cells with higher basal autophagic activity are associated with low ERE levels, and vice versa. Additionally, we downloaded data from previously published studies performing autophagy inhibitions [ 51 , 52 ] and observed that autophagy inhibition, whether genetic or chemical, resulted systematically in the upregulation of EREs (Fig. 5F ).…”

The Role of Autophagy in Vascular Endothelial Cell Health and Physiology

“…The inhibition of autophagy in these cells impaired VEGF-induced angiogenesis [80,81]. In mice, ATG5 deficiency also leads to impaired VEGF-and flow-mediated neoangiogenesis in both microvascular and macrovascular beds [82]. Further work is needed to elucidate autophagy's exact function in vessel development.…”