| First Author | Piao S | Year | 2018 |
| Journal | PLoS One | Volume | 13 |
| Issue | 2 | Pages | e0192693 |
| PubMed ID | 29474366 | Mgi Jnum | J:260425 |
| Mgi Id | MGI:6140362 | Doi | 10.1371/journal.pone.0192693 |
| Citation | Piao S, et al. (2018) CR6 interacting factor 1 deficiency promotes endothelial inflammation by SIRT1 downregulation. PLoS One 13(2):e0192693 |
| abstractText | AIMS: CR6 interacting factor 1 (CRIF1) deficiency impairs mitochondrial oxidative phosphorylation complexes, contributing to increased mitochondrial and cellular reactive oxygen species (ROS) production. CRIF1 downregulation has also been revealed to decrease sirtuin 1 (SIRT1) expression and impair vascular function. Inhibition of SIRT1 disturbs oxidative energy metabolism and stimulates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB)-induced inflammation. Therefore, we hypothesized that both CRIF1 deficiency-induced mitochondrial ROS production and SIRT1 reduction play stimulatory roles in vascular inflammation. METHODS AND RESULTS: Plasma levels and mRNA expression of proinflammatory cytokines (tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6) were markedly elevated in endothelium-specific CRIF1-knockout mice and CRIF1-silenced endothelial cells, respectively. Moreover, CRIF1 deficiency-induced vascular adhesion molecule-1 (VCAM-1) expression was consistently attenuated by the antioxidant N-acetyl-cysteine and NF-kappaB inhibitor (BAY11). We next showed that siRNA-mediated CRIF1 downregulation markedly activated NF-kappaB. SIRT1 overexpression not only rescued CRIF1 deficiency-induced NF-kappaB activation but also decreased inflammatory cytokines (TNF-alpha, IL-1beta, and IL-6) and VCAM-1 expression levels in endothelial cells. CONCLUSIONS: These results strongly suggest that CRIF1 deficiency promotes endothelial cell inflammation by increasing VCAM-1 expression, elevating inflammatory cytokines levels, and activating the transcription factor NF-kappaB, all of which were inhibited by SIRT1 overexpression. |
