Using genetically modified mice harboring fluorescent cell lineage tracers, single-cell RNA-Seq, and long-term inhibition of RAS in both mice and humans, we tested (a) whether renin cells were directly involved in the arterial disease, (b) whether renin cells changed their identity and were transformed during the evolution of the arterial pathology, (c) whether renin cells synthesized factors that modify the composition of the extracellular milieu responsible for the arterial disease, and (d) whether a similar arterial disease was observed in humans treated with RASi. Here, REN is linked to arterial disorder.