Proline/serine-rich coiled-coil 1 alleviates atherosclerosis via remodeling tryptophan metabolism mediated by Akkermansia muciniphila - PubMed
5 days ago
- #Atherosclerosis
- #Tryptophan metabolism
- #PSRC1
- PSRC1 is implicated in coronary artery disease (CAD) pathogenesis.
- Psrc1 deficiency accelerates atherosclerosis via gut microbial dysbiosis, particularly depleting Akkermansia muciniphila.
- Akkermansia muciniphila regulates tryptophan metabolism, influencing immune responses in atherosclerosis.
- Psrc1 knockout mice show reduced mucin, altered tryptophan enzymes, and lower Trp metabolites like IAA, suppressing Ahr signaling.
- Psrc1 stabilizes Ahr protein via Uchl3-mediated deubiquitylation.
- Plasma IAA levels correlate with decreased PSRC1 expression in CAD patients.
- Oral A. muciniphila-IAA supplementation reverses atherosclerosis in Psrc1 knockout mice by reducing macrophage apoptosis.
- Ahr antagonist CH-223191 negates the benefits, confirming Ahr's role.
- PSRC1 regulates the A. muciniphila-IAA-Ahr axis, suggesting microbiome-targeted Ahr activation as a CAD therapy.