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Publication
Dysregulated oxalate metabolism is a driver and therapeutic target in
atherosclerosis.
Authors Liu Y, Zhao Y, Shukha Y, Lu H, Wang L, Liu Z, Liu C, Zhao Y, Wang H, Zhao G,
Liang W, Fan Y, Chang L, Yurdagul A, Pattillo CB, Orr AW, Aviram M, Wen B,
Garcia-Barrio MT, Zhang J, Liu W, Sun D, Hayek T, Chen YE, Rom O
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Cell reports
Year 2021
Date Published 7/1/2021
Volume : Pages 36 : 109420
PubMed Reference 34320345
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.




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