There has been intense recent interest in the possibility that inhibition of EndMT may be a viable clinical approach to treat various cardiovascular diseases.15,16,20,21 However, despite many positive studies in small animals, there have been no dedicated translational attempts to investigate this possibility in a large animal model.15,16,20,21 Here, based on our earlier studies in mice,14 we created a large animal AVF model and investigated the effect of EndMT inhibition by local knockdown of SMAD3, with a specific view towards understanding the likely clinical utility of this approach. Here, SMAD3 is linked to cardiovascular disorder.