| First Author | Liu Y | Year | 2021 |
| Journal | Cell Rep | Volume | 36 |
| Issue | 4 | Pages | 109420 |
| PubMed ID | 34320345 | Mgi Jnum | J:321711 |
| Mgi Id | MGI:6876888 | Doi | 10.1016/j.celrep.2021.109420 |
| Citation | Liu Y, et al. (2021) Dysregulated oxalate metabolism is a driver and therapeutic target in atherosclerosis. Cell Rep 36(4):109420 |
| abstractText | Dysregulated glycine metabolism is emerging as a common denominator in cardiometabolic diseases, but its contribution to atherosclerosis remains unclear. In this study, we demonstrate impaired glycine-oxalate metabolism through alanine-glyoxylate aminotransferase (AGXT) in atherosclerosis. As found in patients with atherosclerosis, the glycine/oxalate ratio is decreased in atherosclerotic mice concomitant with suppression of AGXT. Agxt deletion in apolipoprotein E-deficient (Apoe(-/-)) mice decreases the glycine/oxalate ratio and increases atherosclerosis with induction of hepatic pro-atherogenic pathways, predominantly cytokine/chemokine signaling and dysregulated redox homeostasis. Consistently, circulating and aortic C-C motif chemokine ligand 5 (CCL5) and superoxide in lesional macrophages are increased. Similar findings are observed following dietary oxalate overload in Apoe(-/-) mice. In macrophages, oxalate induces mitochondrial dysfunction and superoxide accumulation, leading to increased CCL5. Conversely, AGXT overexpression in Apoe(-/-) mice increases the glycine/oxalate ratio and decreases aortic superoxide, CCL5, and atherosclerosis. Our findings uncover dysregulated oxalate metabolism via suppressed AGXT as a driver and therapeutic target in atherosclerosis. |
