| First Author | Da Ros F | Year | 2017 |
| Journal | Immunity | Volume | 47 |
| Issue | 5 | Pages | 959-973.e9 |
| PubMed ID | 29150241 | Mgi Jnum | J:259006 |
| Mgi Id | MGI:6142031 | Doi | 10.1016/j.immuni.2017.10.016 |
| Citation | Da Ros F, et al. (2017) Targeting Interleukin-1beta Protects from Aortic Aneurysms Induced by Disrupted Transforming Growth Factor beta Signaling. Immunity 47(5):959-973.e9 |
| abstractText | Aortic aneurysms are life-threatening conditions with effective treatments mainly limited to emergency surgery or trans-arterial endovascular stent grafts, thus calling for the identification of specific molecular targets. Genetic studies have highlighted controversial roles of transforming growth factor beta (TGF-beta) signaling in aneurysm development. Here, we report on aneurysms developing in adult mice after smooth muscle cell (SMC)-specific inactivation of Smad4, an intracellular transducer of TGF-beta. The results revealed that Smad4 inhibition activated interleukin-1beta (IL-1beta) in SMCs. This danger signal later recruited innate immunity in the adventitia through chemokine (C-C motif) ligand 2 (CCL2) and modified the mechanical properties of the aortic wall, thus favoring vessel dilation. SMC-specific Smad4 deletion in Il1r1- or Ccr2-null mice resulted in milder aortic pathology. A chronic treatment with anti-IL-1beta antibody effectively hampered aneurysm development. These findings identify a mechanistic target for controlling the progression of aneurysms with compromised TGF-beta signaling, such as those driven by SMAD4 mutations. |
