While endothelial dysfunction and TGFβ hyperactivity appear to be prominent primary and secondary consequences of a fibrillin-1 deficiency, respectively, we can only speculate that the ECM defect increases both pressure-induced intramural stress and flow-induced shear stress, with the result of perturbing the ability of resident cells to maintain aortic wall homeostasis. This evidence concerns the gene TGFB1 and endothelial dysfunction.