| First Author | Otsuka G | Year | 2006 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 26 |
| Issue | 4 | Pages | 737-43 |
| PubMed ID | 16373605 | Mgi Jnum | J:127967 |
| Mgi Id | MGI:3765281 | Doi | 10.1161/01.ATV.0000201087.23877.e1 |
| Citation | Otsuka G, et al. (2006) Transforming growth factor beta 1 induces neointima formation through plasminogen activator inhibitor-1-dependent pathways. Arterioscler Thromb Vasc Biol 26(4):737-43 |
| abstractText | OBJECTIVE: The mechanisms through which transforming growth factor (TGF)-beta1 promotes intimal growth, and the pathways through which TGF-beta1 expression is regulated in the artery wall, are incompletely understood. We used a mouse model to investigate mechanisms of TGF-beta1-induced intimal growth. METHODS AND RESULTS: Adenovirus-mediated overexpression of TGF-beta1 in uninjured carotid arteries of wild-type mice induced formation of a cellular and matrix-rich intima. Intimal growth appeared primarily due to cell migration and matrix accumulation, with only a negligible contribution from cell proliferation. Overexpression of TGF-beta1 also stimulated expression of plasminogen activator inhibitor type 1 (plasminogen activator inhibitor [PAI]-1) in the artery wall. To test the hypothesis that PAI-1 is a critical downstream mediator of TGF-beta1-induced intimal growth, we transduced carotid arteries of PAI-1-deficient (Serpine1(-/-)) mice with the TGF-beta1-expressing vector. Overexpression of TGF-beta1 in Serpine1(-/-) arteries did not increase intimal growth, matrix accumulation, cell migration, or proliferation. Moreover, TGF-beta1-transduced arteries of Serpine1(-/-) mice secreted 6- to 10-fold more TGF-beta1 than did arteries of wild-type mice that were infused with the same concentration of the TGF-beta1-expressing vector. CONCLUSIONS: PAI-1 is both a critical mediator of TGF-beta1-induced intimal growth and a key negative regulator of TGF-beta1 expression in the artery wall. |
