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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 β (TGF-β) 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-β. The results revealed that Smad4 inhibition activated interleukin-1β (IL-1β) 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-1β antibody effectively hampered aneurysm development. These findings identify a mechanistic target for controlling the progression of aneurysms with compromised TGF-β signaling, such as those driven by SMAD4 mutations.
Pubmed ID: 29150241 RIS Download
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This monoclonal targets CD49b/Pan-NK Cells
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis monoclonal targets CD45R / B220
View all literature mentionsThis polyclonal targets Smad4 (H-552)
View all literature mentionsThis unknown targets Rat
View all literature mentionsThis monoclonal targets CD16/CD32
View all literature mentionsThis polyclonal targets Phospho-Myosin Light Chain 2 (Ser19)
View all literature mentionsThis polyclonal targets IL1 Receptor I antibody
View all literature mentionsThis polyclonal targets IL1 beta
View all literature mentionsThis monoclonal targets alpha smooth muscle Actin
View all literature mentionsThis polyclonal targets RELA
View all literature mentionsThis monoclonal targets CD90.2
View all literature mentionsThis polyclonal targets Phospho-SAPK/JNK (Thr183/Tyr185)
View all literature mentionsThis unknown targets Collagen type I
View all literature mentionsThis monoclonal targets NK-1.1
View all literature mentionsThis polyclonal targets Phospho-Smad2 (Ser465/467)
View all literature mentionsThis monoclonal targets Actin, alpha, Smooth Muscle
View all literature mentionsThis polyclonal targets Mapk3
View all literature mentionsThis monoclonal targets NF-KappaB p65, phospho (Ser536)
View all literature mentionsThis polyclonal targets phosphoSmad1/Smad5/Smad8 phospho-specific (Ser463/465)
View all literature mentionsThis monoclonal targets TER-119/Erythroid Cells
View all literature mentionsThis monoclonal targets Ly-6G
View all literature mentionsThis monoclonal targets Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb
View all literature mentionsThis monoclonal targets Mouse IL-1 beta/IL-1F2 Phycoerythrin MAb (Clone 166931)
View all literature mentionsThis polyclonal targets IgG-heavy and light chain
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis isotype control targets Unknown Specificity
View all literature mentionsThis polyclonal targets Sars
View all literature mentionsThis polyclonal targets IgG-heavy and light chain
View all literature mentionsThis monoclonal targets Mouse CD11b
View all literature mentionsThis monoclonal targets CD3
View all literature mentionsThis polyclonal targets MYH11
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis monoclonal targets F4/80
View all literature mentionsThis monoclonal targets
View all literature mentionsThis polyclonal targets PPP1R12A
View all literature mentionsThis monoclonal targets MRCL3/MRLC2 (A-10)
View all literature mentionsThis unknown targets TAK1, phospho (Thr184 / Thr187)
View all literature mentionsThis monoclonal targets Mouse CD68
View all literature mentionsThis monoclonal targets Mouse CD45
View all literature mentionsMus musculus with name B6.129S4-Ccr2tm1Ifc/J from IMSR.
View all literature mentionsMus musculus with name B6.129(Cg)-Il1r1tm1.1Rbl/J from IMSR.
View all literature mentionsMus musculus with name B6.129S4-Ccr2tm1Ifc/J from IMSR.
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis isotype control targets Unknown Specificity
View all literature mentionsThis monoclonal targets TER-119/Erythroid Cells
View all literature mentionsThis monoclonal targets NK-1.1
View all literature mentionsThis monoclonal targets Ly-6G
View all literature mentionsThis monoclonal targets Mouse IL-1 beta/IL-1F2 Phycoerythrin MAb (Clone 166931)
View all literature mentionsThis unknown targets Rat
View all literature mentionsThis monoclonal targets CD90.2
View all literature mentionsThis monoclonal targets CD49b/Pan-NK Cells
View all literature mentionsThis monoclonal targets CD45R / B220
View all literature mentionsThis monoclonal targets alpha smooth muscle Actin
View all literature mentionsThis monoclonal targets CD16/CD32
View all literature mentionsThis monoclonal targets F4/80
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis polyclonal targets IgG-heavy and light chain
View all literature mentionsThis polyclonal targets IgG-heavy and light chain
View all literature mentionsThis unknown targets Rat IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal targets RELA
View all literature mentionsThis polyclonal targets Phospho-Smad2 (Ser465/467)
View all literature mentionsThis polyclonal targets phosphoSmad1/Smad5/Smad8 phospho-specific (Ser463/465)
View all literature mentionsThis monoclonal targets Phospho-p38 MAPK (Thr180/Tyr182) (3D7) Rabbit mAb
View all literature mentionsThis polyclonal targets Phospho-Myosin Light Chain 2 (Ser19)
View all literature mentionsThis polyclonal targets Phospho-SAPK/JNK (Thr183/Tyr185)
View all literature mentionsThis monoclonal targets NF-KappaB p65, phospho (Ser536)
View all literature mentionsThis polyclonal targets Mapk3
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis polyclonal targets Sars
View all literature mentionsThis monoclonal targets
View all literature mentionsThis monoclonal targets CD3
View all literature mentionsThis monoclonal targets Mouse CD11b
View all literature mentionsThis polyclonal targets Smad4 (H-552)
View all literature mentionsThis polyclonal targets IL1 Receptor I antibody
View all literature mentionsThis polyclonal targets IL1 beta
View all literature mentionsThis unknown targets Collagen type I
View all literature mentionsThis monoclonal targets Actin, alpha, Smooth Muscle
View all literature mentionsThis polyclonal targets PPP1R12A
View all literature mentionsThis monoclonal targets MRCL3/MRLC2 (A-10)
View all literature mentionsThis unknown targets TAK1, phospho (Thr184 / Thr187)
View all literature mentionsThis monoclonal targets Mouse CD68
View all literature mentionsThis monoclonal targets Mouse CD45
View all literature mentionsThis monoclonal targets CD3
View all literature mentionsThis monoclonal targets Mouse CD11b
View all literature mentionsThis polyclonal targets phosphoSmad1/Smad5/Smad8 phospho-specific (Ser463/465)
View all literature mentionsThis polyclonal targets phosphoSmad1/Smad5/Smad8 phospho-specific (Ser463/465)
View all literature mentionsThis polyclonal targets MYH11
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