SMAD3 and aneurysm: Our own work and that of others has shown that these two types of VSMCs respond differently to aneurysm-causing mutations, including those that cause Smad3 deficiency, and suggested the possibility that their peculiar distribution in the aortic root and ascending aorta may underlie regional susceptibility to aneurysmal disease (11, 84, 110, 113–115) (Supplementary Figure 5).