Although the SRF/myocardin pathway has been reported as primarily regulating cytoskeletal proteins and involved in VSMC differentiation and stiffness (Zhou, Lee, Stoll, Ma, Wiener, et al. 2017), our data from this study demonstrate that SRF/myocardin signaling also participates in VSMC‐medicated extracellular dysregulation in hypertension, bringing new insight into the mechanism integrating intra‐ and extracellular function of VSMCs in aortic stiffening. Here, MYOCD is linked to hypertensive disorder.