Unknown

Dataset Information

0

Dysregulated oxalate metabolism is a driver and therapeutic target in atherosclerosis.


ABSTRACT: 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.

SUBMITTER: Liu Y 

PROVIDER: S-EPMC8363062 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications


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<sup>-/-</sup>)  ...[more]

Similar Datasets

| S-EPMC5350105 | biostudies-other
| S-EPMC6232824 | biostudies-literature
2025-07-16 | GSE298392 | GEO
| S-EPMC7610885 | biostudies-literature
| S-EPMC6722844 | biostudies-literature
| S-SCDT-10_1038-S44321-024-00186-Z | biostudies-other
| S-EPMC6302344 | biostudies-literature
| S-EPMC10045916 | biostudies-literature
| S-EPMC3175103 | biostudies-literature
| PRJNA1269065 | ENA