Loss of Endothelial Barrier in Marfan Mice (mgR/mgR) Results in Severe Inflammation after Adenoviral Gene Therapy
A-E: Van Gieson stain of 30-day old mouse aortic grafts after heterotopic infrarenal transplantation (40x magnification). WT grafts point out almost no (A, NI = 1.24%) and native mgR/mgR Marfan grafts just a minor stenosis of the lumen (NI = 5.7%). Marfan graft after treatment with adenoviral vectors coding for β-galactosidase (C, NI = 23.05%) and hTIMP-1 (D, 43,45%) display intimal hyperplasia narrowing the lumen (p = 0.038). In contrast, wildtype vessels do not present intimal hyperplasia after transduction with Ad.hTIMP-1 (E, NI = 0.00%). F: Mean of neointimal index in 30-day old transplanted aortas (n = 7). Compared to native mgR/mgR grafts NI is significant greater in Ad.hTIMP-1 (p = 0.026) and borderline significant in Ad.β-Gal. transduced mgR/mgR grafts (p = 0.053). WT, wildtype aorta; mgR/mgR, Marfan aorta; Ad.β-Gal, treated with adenovirus coding for β-galactosidase; Ad.hTIMP-1, treated with adenovirus coding for human TIMP-1; NI, neointimal index, neointima / (neointima + lumen). *p-value ≤0.05; ** p-value ≤0.001, calculated using Mann-Whitney-U-Test (n = 7).