Journal: Angiogenesis
Article Title: Genetic and pharmacological targeting of mTORC1 in mouse models of arteriovenous malformation expose non-cell autonomous signalling in HHT
doi: 10.1007/s10456-024-09961-5
Figure Lengend Snippet: EC-specific overactivation of mTORC1 reduces incidence and thickness of AVMs induced by blocking antibodies. A . Time scheme for administration of tamoxifen, BMP9/10 blocking antibodies (bAbs)/Isotype IgG, and sample collection. B . Representative pictures showing retinal vasculatures of control (Cre-) and Tsc1 iECKO mice treated with IgGs or anti-BMP9/10 antibodies (Abs). Arrows indicate AVMs. C . Quantification of number of AVMs per retina of Control ( n = 5 mice) and Tsc1 iECKO ( n = 5 mice) mice treated with anti-BMP9/10 Abs. D . Quantification of AVM thickness in Control ( n = 5 mice) and Tsc1 iECKO mice ( n = 3) treated with IgGs or anti-BMP9/10 Abs. E . Central retinal vasculatures of control (Cre-) and Tsc1 iECKO mice, treated with anti-BMP9/10 Abs, immunolabelled for CD31, p-RPS6, and YFP (indicative of recombination). F . Quantification of the ratio of the p-RPS6 + area within the CD31 + area to the complete CD31 + area ( F ), as well as the p-RPS6 + area outside the CD31 + area to the complete non-vascular area ( G ) of central retinas of Control ( n = 3 mice) and Tsc1 iECKO ( n = 3 mice) mice treated with anti-BMP9/10 Abs. Note the vascular specific increase of p-RPS6, indicative of EC-specific mTORC1 overactivation. All data was analysed by two-tailed unpaired t-test with Welch’s correction. Bars indicate mean ± s.d. * p < 0.05
Article Snippet: Pups were treated with mouse monoclonal antibodies against BMP9 and BMP10 (15 mg/kg, IgG2b, MAB3209; 15 mg/kg, IgG2a, MAB2926; R&D Systems, respectively) or isotype control antibodies (15 mg/kg, IgG2b, MAB004; 15 mg/kg, IgG2a, MAB003; R&D Systems, respectively) at P3, P4 and P5 and tissues were harvested at P6.
Techniques: Blocking Assay, Control, Two Tailed Test