Houkin et al. proposed a double hit hypothesis in which, in addition to the mutation in RNF213, some triggers such as hemodynamic stress, ischemia, infection or immune disorder are essential in starting the first step in the pathological process of the disease.[20] Although we showed in this study the nature of endothelial cells of MMD under ordinary culture conditions, future analysis of the cell function of MMD under shear stress or hypoxic conditions may clarify the mechanism that leads to the development of MMD. This evidence concerns the gene RNF213 and ischemia.