Autophagy protein 5 controls flow-dependent endothelial functions

Cell Mol Life Sci. 2023 Jul 18;80(8):210. doi: 10.1007/s00018-023-04859-9.


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.

Keywords: Autophagy; Endothelium; Flow-mediated dilatation; Mechanosensing; VEGFR2; eNOS.

MeSH terms

  • Animals
  • Autophagy
  • Autophagy-Related Protein 5 / genetics
  • Autophagy-Related Protein 5 / metabolism
  • Endothelial Cells* / metabolism
  • Endothelium, Vascular / metabolism
  • Humans
  • Mesenteric Arteries / metabolism
  • Mice
  • Myocardial Infarction* / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Signal Transduction
  • Vasodilation


  • Autophagy-Related Protein 5
  • Nitric Oxide Synthase Type III