| First Author | Su E | Year | 2022 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 42 |
| Issue | 3 | Pages | 305-325 |
| PubMed ID | 35045729 | Mgi Jnum | J:360465 |
| Mgi Id | MGI:7797591 | Doi | 10.1161/ATVBAHA.121.317339 |
| Citation | Su E, et al. (2022) Endothelial Intracellular ANG (Angiogenin) Protects Against Atherosclerosis by Decreasing Endoplasmic Reticulum Stress. Arterioscler Thromb Vasc Biol 42(3):305-325 |
| abstractText | BACKGROUND: ANG (angiogenin) is essential for cellular adaptation to endoplasmic reticulum (ER) stress, a process closely associated with cardiovascular diseases, including atherosclerosis. We aimed to investigate the role of ANG in the progression of atherosclerosis and elucidate its underlying molecular mechanisms. METHODS: We constructed adenoassociated virus 9 ANG overexpression vectors and endothelial ANG- and ApoE (apolipoprotein E)-deficient mice to determine the effects of ANG on ER stress and atherosclerotic lesions. RNA sequencing of endothelial ANG- and ApoE-deficient mice identified ANG-dependent downregulation of ST3GAL5 (ST3 beta-galactoside alpha-2,3-sialyltransferase 5) expression, and the direct regulation of ST3GAL5 by ANG was verified by chromatin immunoprecipitation sequencing and luciferase reporter assay results. RESULTS: Reanalysis of expression profiling datasets indicated decreased ANG levels in patients' atherosclerotic lesions, and these data were validated in aortas from ApoE(-/-) mice. ER stress marker and adhesion molecule levels, aortic root lesions and macrophage deposition were substantially reduced in ApoE(-/-) mice injected with an adenoassociated virus 9 ANG without signal peptide (ANG-DeltaSP) overexpression vector compared with empty and full-length ANG overexpression vectors. Endothelial ANG deficiency significantly elevated ER stress and increased adhesion molecule expression, which aggravated atherosclerotic lesions and enhanced THP-1 monocyte adhesion to endothelial cells in vivo and in vitro, respectively. Furthermore, ANG-DeltaSP overexpression significantly attenuated oxidized low-density lipoprotein-induced ER stress and THP-1 monocyte adhesion to endothelial cells, which were reversed by ST3GAL5 inhibition. CONCLUSIONS: These results suggest that endothelial intracellular ANG is a novel therapeutic against atherosclerosis and exerts atheroprotective effects via ST3GAL5-mediated ER stress suppression. |
