| First Author | Guo G | Year | 2013 |
| Journal | Aorta (Stamford) | Volume | 1 |
| Issue | 1 | Pages | 5-12 |
| PubMed ID | 26798667 | Mgi Jnum | J:299051 |
| Mgi Id | MGI:6490103 | Doi | 10.12945/j.aorta.2013.13.007 |
| Citation | Guo G, et al. (2013) Indomethacin Prevents the Progression of Thoracic Aortic Aneurysm in Marfan Syndrome Mice. Aorta (Stamford) 1(1):5-12 |
| abstractText | BACKGROUND: Marfan syndrome (MFS), an inherited disorder of connective tissue characterized by abnormalities in the skeletal, ocular, and cardiovascular systems, is caused by mutations in the gene for fibrillin-1 (FBN1). The high mortality in untreated patients is primarily due to aneurysm and dissection of the ascending aorta. The complex pathogenesis of MFS involves changes in transforming growth factor beta (TGF-beta) signaling, increased matrix metalloproteinase (MMP) expression, and fragmentation of the extracellular matrix. A number of studies have demonstrated increased counts of macrophages and T cells in the ascending aorta of persons or mouse models of MFS, but the efficacy of anti-inflammatory therapy in mouse models of MFS has not yet been assessed. METHODS: FBN1 underexpressing mgR/mgR Marfan mice were treated with oral indomethacin. Treatment was begun at the age of three weeks and continued for 8 weeks, following which the aorta of wild type as well as treated and untreated mgR/mgR mice was compared. RESULTS: Indomethacin treatment led to a statistically significant reduction of aortic elastin degeneration and macrophage infiltration, as well as a lessening of MMP-2, MMP-9, and MMP-12 upregulation. Additionally, indomethacin decreased both cyclooxygenases 2 (COX-2) expression and activity in the aorta of mgR/mgR mice. COX-2-mediated inflammatory infiltrate contributes to the progression of aortic aneurysm in mgR/mgR mice, providing evidence that COX-2 is a relevant therapeutic target in MFS-associated aortic aneurysmal disease. CONCLUSIONS: COX-2 mediated inflammatory infiltration plays an important role in the pathogenesis of aortic aneurysm disease in MFS. |
