Unknown

Dataset Information

0

Blocking interferon {beta} stimulates vascular smooth muscle cell proliferation and arteriogenesis.


ABSTRACT: Increased interferon (IFN)-? signaling in patients with insufficient coronary collateralization and an inhibitory effect of IFN? on collateral artery growth in mice have been reported. The mechanisms of IFN?-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 IFN?-regulated genes. Immunohistochemically, the IFN? receptor was localized in the vascular media of murine collateral arteries. Treatment of vascular smooth muscle cells (VSMC) with IFN? resulted in an attenuated proliferation, cell-cycle arrest, and increased expression of cyclin-dependent kinase inhibitor-1A (p21). The growth inhibitory effect of IFN? was attenuated by inhibition of p21 by RNA interference. IFN?-treated THP1 monocytes showed enhanced apoptosis. Subsequently, we tested if collateral artery growth can be stimulated by inhibition of IFN?-signaling. RNA interference of the IFN? receptor-1 (IFNAR1) increased VSMC proliferation, cell cycle progression, and reduced p21 gene expression. IFN? 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 IFN? inhibits collateral artery growth and VSMC proliferation through p21-dependent cell cycle arrest and induction of monocyte apoptosis. Inhibition of IFN? stimulates VSMC proliferation and collateral artery growth.

SUBMITTER: Schirmer SH 

PROVIDER: S-EPMC2966083 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

Blocking interferon {beta} stimulates vascular smooth muscle cell proliferation and arteriogenesis.

Schirmer Stephan H SH   Bot Pieter T PT   Fledderus Joost O JO   van der Laan A M AM   Volger Oscar L OL   Laufs Ulrich U   Böhm Michael M   de Vries Carlie J M CJ   Horrevoets Anton J G AJ   Piek Jan J JJ   Hoefer Imo E IE   van Royen Niels N  

The Journal of biological chemistry 20100824 45


Increased interferon (IFN)-β signaling in patients with insufficient coronary collateralization and an inhibitory effect of IFNβ on collateral artery growth in mice have been reported. The mechanisms of IFNβ-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 IFNβ-regulated genes. Immunohistochemically, the IFNβ rece  ...[more]

Similar Datasets

| S-EPMC2724222 | biostudies-other
| S-EPMC2742749 | biostudies-literature
| S-EPMC9254254 | biostudies-literature
| S-EPMC9468459 | biostudies-literature
| S-EPMC5276722 | biostudies-literature
| S-EPMC4746734 | biostudies-literature
| S-EPMC6359109 | biostudies-literature
| S-EPMC4866761 | biostudies-literature
| S-EPMC3939657 | biostudies-literature
| S-EPMC4314658 | biostudies-literature