| First Author | Hara H | Year | 2020 |
| Journal | PLoS One | Volume | 15 |
| Issue | 11 | Pages | e0239908 |
| PubMed ID | 33175881 | Mgi Jnum | J:297559 |
| Mgi Id | MGI:6473638 | Doi | 10.1371/journal.pone.0239908 |
| Citation | Hara H, et al. (2020) Inhibition of transforming growth factor-beta signaling in myeloid cells ameliorates aortic aneurysmal formation in Marfan syndrome. PLoS One 15(11):e0239908 |
| abstractText | Increased transforming growth factor-beta (TGF-beta) signaling contributes to the pathophysiology of aortic aneurysm in Marfan syndrome (MFS). Recent reports indicate that a small but significant number of inflammatory cells are infiltrated into the aortic media and adventitia in MFS. However, little is known about the contribution of myeloid cells to aortic aneurysmal formation. In this study, we ablated the TGF-beta type II receptor gene Tgfbr2 in myeloid cells of Fbn1C1039G/+ MFS mice (Fbn1C1039G/+;LysM-Cre/+;Tgfbr2fl/fl mice, hereinafter called Fbn1C1039G/+;Tgfbr2MyeKO) and evaluated macrophage infiltration and TGF-beta signaling in the aorta. Aneurysmal formation with fragmentation and disarray of medial elastic fibers observed in MFS mice was significantly ameliorated in Fbn1C1039G/+;Tgfbr2MyeKO mice. In the aorta of Fbn1C1039G/+;Tgfbr2MyeKO mice, both canonical and noncanonical TGF-beta signals were attenuated and the number of infiltrated F4/80-positive macrophages was significantly reduced. In vitro, TGF-beta enhanced the migration capacity of RAW264.7 macrophages. These findings suggest that TGF-beta signaling in myeloid cells promotes aortic aneurysmal formation and its inhibition might be a novel therapeutic target in MFS. |
