| First Author | Nosaka M | Year | 2011 |
| Journal | J Clin Invest | Volume | 121 |
| Issue | 7 | Pages | 2911-20 |
| PubMed ID | 21646723 | Mgi Jnum | J:175655 |
| Mgi Id | MGI:5286810 | Doi | 10.1172/JCI40782 |
| Citation | Nosaka M, et al. (2011) Absence of IFN-gamma accelerates thrombus resolution through enhanced MMP-9 and VEGF expression in mice. J Clin Invest 121(7):2911-20 |
| abstractText | Deep vein thrombosis (DVT) is a major cause of pulmonary thromboembolism, a leading cause of death in individuals with DVT. Several lines of evidence indicate proinflammatory cytokines such as TNF-alpha are involved in thrombus formation and resolution, but the roles of IFN-gamma remain unclear. To address this issue, we performed ligation of the inferior vena cava to induce DVT in WT and IFN-gamma-deficient (Ifng-/-) mice. In WT mice, intrathrombotic IFN-gamma levels were elevated progressively as the postligation interval was extended. Thrombus size was substantially smaller at 10 and 14 days in Ifng-/- mice than in WT mice. Intrathrombotic collagen content was remarkably reduced at more than 10 days after the ligation in Ifng-/- mice compared with WT mice. The expression and activity of MMP-9, but not MMP-2, was higher at the late phase in Ifng-/- mice than in WT mice. Moreover, intrathrombotic recanalization was increased in Ifng-/- mice, with enhanced Vegf gene expression, compared with that in WT mice. Activation of the IFN-gamma/Stat1 signal pathway suppressed PMA-induced Mmp9 and Vegf gene expression in peritoneal macrophages. Furthermore, administration of anti-IFN-gamma mAbs accelerated thrombus resolution in WT mice. Collectively, these findings indicate that IFN-gamma can have detrimental roles in thrombus resolution and may be a good molecular target for the acceleration of thrombus resolution in individuals with DVT. |
