| First Author | Isoda K | Year | 2003 |
| Journal | Circulation | Volume | 108 |
| Issue | 5 | Pages | 516-8 |
| PubMed ID | 12874179 | Mgi Jnum | J:103068 |
| Mgi Id | MGI:3608426 | Doi | 10.1161/01.CIR.0000085567.18648.21 |
| Citation | Isoda K, et al. (2003) Deficiency of interleukin-1 receptor antagonist promotes neointimal formation after injury. Circulation 108(5):516-8 |
| abstractText | BACKGROUND: The cytokine interleukin (IL)-1 is an important mediator of inflammation and cardiovascular disease. Activity of this cytokine is modulated endogenously via the IL-1 receptor antagonist (IL-1Ra). The role of IL-1Ra in neointima formation after injury, however, is poorly understood. METHODS AND RESULTS: Using IL-1Ra-deficient (IL-1Ra-/-; backcrossed 8 generations into the C57BL/6J background) and wild-type (IL-1Ra+/+) mice, we investigated neointimal formation 3 weeks after femoral artery injury induced by an external vascular cuff model. Intima and media thicknesses were measured, and the intima/media ratio was calculated. The mean intimal thickness and the intima/media ratio of IL-1Ra-/- mice increased by 249% (31.8+/-2.9 microm [n=10] versus 9.1+/-0.7 microm [n=10]; P<0.0001) and 257% (2.5+/-0.2 versus 0.7+/-0.1; P<0.0001), respectively, compared with IL-1Ra+/+ mice. No significant differences were observed in the medial thickness. Control immunostaining for IL-1Ra in injured vessels localized IL-1beta and the endogenous inhibitor in the endothelium and inflammatory cells of the adventitia in IL-1Ra+/+ but not IL-1Ra-/- mice. CONCLUSIONS: The absence of IL-1Ra promotes neointimal formation in mice after injury. These results suggest that endogenous IL-1Ra may suppress other occlusive vascular responses to injury, such as atherosclerosis and restenosis after angioplasty. |
