| First Author | Niida T | Year | 2012 |
| Journal | Cardiovasc Res | Volume | 93 |
| Issue | 2 | Pages | 371-9 |
| PubMed ID | 22135163 | Mgi Jnum | J:194870 |
| Mgi Id | MGI:5474927 | Doi | 10.1093/cvr/cvr323 |
| Citation | Niida T, et al. (2012) IkappaBNS regulates interleukin-6 production and inhibits neointimal formation after vascular injury in mice. Cardiovasc Res 93(2):371-9 |
| abstractText | AIMS: IkappaBNS regulates a subset of Toll-like receptor (TLR)-dependent genes including interleukin-6 (IL-6) by inhibiting nuclear factor-kappaB (NF-kappaB). IL-6 is an inflammatory biomarker for cardiovascular diseases. The aim of this study was to determine whether IkappaBNS changes arterial inflammation and intimal hyperplasia after vascular injury. METHODS AND RESULTS: We investigated neointimal formation in IkappaBNS-deficient (IkappaBNS(-/-); C57BL/6 background) and wild-type (IkappaBNS(+/+)) mice 2 weeks after cuff injury. The mean intimal area and the intima/media ratio of IkappaBNS(-/-) mice increased 89% (8066 +/- 1141 vs. 4267 +/- 1095 mum(2); P = 0.027) and 100% (0.72 +/- 0.13 vs. 0.36 +/- 0.09; P = 0.032) compared with IkappaBNS(+/+) mice. We observed significant up-regulation of TLR4 in injured arteries of IkappaBNS(-/-) mice. NF-kappaB activity in the intima of IkappaBNS(-/-) mice was 5.1-fold higher (P = 0.008) compared with IkappaBNS(+/+) mice at 7 days post-injury. IL-6 mRNA levels in injured arteries of IkappaBNS(-/-) mice were 1.8-fold higher (P = 0.002) compared with those of IkappaBNS(+/+) mice at 3 days post-injury. Vascular smooth muscle cells from IkappaBNS(-/-) mice showed a significant increase in cell migration compared with those from IkappaBNS(+/+) mice after IL-6 stimulation in the scratch-wound healing assay. Furthermore, anti-mouse IL-6 receptor antibody (MR16-1) significantly reduced intimal hyperplasia compared with control IgG injection in IkappaBNS(-/-) mice. These findings suggest that IL-6 participates in the development of neointimal hyperplasia after vascular injury in IkappaBNS(-/-) mice. CONCLUSION: IkappaBNS down-regulates TLR4 expression, NF-kappaB activity, and IL-6 production after vascular injury. IkappaBNS might suppress intimal hyperplasia caused by vascular inflammation such as atherosclerosis, and restenosis after angioplasty. |
