| First Author | Liu H | Year | 2022 |
| Journal | Cell Death Dis | Volume | 13 |
| Issue | 4 | Pages | 299 |
| PubMed ID | 35379776 | Mgi Jnum | J:338336 |
| Mgi Id | MGI:7263514 | Doi | 10.1038/s41419-022-04719-7 |
| Citation | Liu H, et al. (2022) PRMT5 critically mediates TMAO-induced inflammatory response in vascular smooth muscle cells. Cell Death Dis 13(4):299 |
| abstractText | A high plasma level of the choline-derived metabolite trimethylamine N-oxide (TMAO) is closely related to the development of cardiovascular disease. However, the underlying mechanism remains unclear. In the present study, we demonstrated that a positive correlation of protein arginine methyltransferase 5 (PRMT5) expression and TMAO-induced vascular inflammation, with upregulated vascular cell adhesion molecule-1 (VCAM-1) expression in primary rat and human vascular smooth muscle cells (VSMC) in vitro. Knockdown of PRMT5 suppressed VCAM-1 expression and the adhesion of primary bone marrow-derived macrophages to TMAO-stimulated VSMC. VSMC-specific PRMT5 knockout inhibited vascular inflammation with decreased expression of VCAM-1 in mice. We further identified that PRMT5 promoted VCAM-1 expression via symmetrical demethylation of Nuclear factor-kappaB p65 on arginine 30 (R30). Finally, we found that TMAO markedly induced the expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) and production of reactive oxygen species, which contributed to PRMT5 expression and subsequent VCAM-1 expression. Collectively, our data provide novel evidence to establish a Nox4-PRMT5-VCAM-1 in mediating TMAO-induced VSMC inflammation. PRMT5 may be a potential target for the treatment of TMAO-induced vascular diseases. |
