| First Author | Schirmer SH | Year | 2010 |
| Journal | J Biol Chem | Volume | 285 |
| Issue | 45 | Pages | 34677-85 |
| PubMed ID | 20736166 | Mgi Jnum | J:167100 |
| Mgi Id | MGI:4867153 | Doi | 10.1074/jbc.M110.164350 |
| Citation | Schirmer SH, et al. (2010) Blocking interferon {beta} stimulates vascular smooth muscle cell proliferation and arteriogenesis. J Biol Chem 285(45):34677-85 |
| abstractText | Increased interferon (IFN)-beta signaling in patients with insufficient coronary collateralization and an inhibitory effect of IFNbeta on collateral artery growth in mice have been reported. The mechanisms of IFNbeta-induced inhibition of arteriogenesis are unknown. In stimulated monocytes from patients with chronic total coronary artery occlusion and decreased arteriogenic response, whole genome expression analysis showed increased expression of IFNbeta-regulated genes. Immunohistochemically, the IFNbeta receptor was localized in the vascular media of murine collateral arteries. Treatment of vascular smooth muscle cells (VSMC) with IFNbeta resulted in an attenuated proliferation, cell-cycle arrest, and increased expression of cyclin-dependent kinase inhibitor-1A (p21). The growth inhibitory effect of IFNbeta was attenuated by inhibition of p21 by RNA interference. IFNbeta-treated THP1 monocytes showed enhanced apoptosis. Subsequently, we tested if collateral artery growth can be stimulated by inhibition of IFNbeta-signaling. RNA interference of the IFNbeta receptor-1 (IFNAR1) increased VSMC proliferation, cell cycle progression, and reduced p21 gene expression. IFNbeta signaling and FAS and TRAIL expression were attenuated in monocytes from IFNAR1(-/-) mice, indicating reduced monocyte apoptosis. Hindlimb perfusion restoration 1 week after femoral artery ligation was improved in IFNAR1(-/-) mice compared with wild-type mice as assessed by infusion of fluorescent microspheres. These results demonstrate that IFNbeta inhibits collateral artery growth and VSMC proliferation through p21-dependent cell cycle arrest and induction of monocyte apoptosis. Inhibition of IFNbeta stimulates VSMC proliferation and collateral artery growth. |
