Notably, key pathways—including ERK signaling, calcium ion transport, integrin‐mediated signaling, ER stress response, oxidative stress response, TLR4 signaling, and ceramide synthesis—exhibited similar changes in the vessel‐on‐a‐chip system and the mouse hypertension model, signifying successful replication of in vivo conditions. This evidence concerns the gene TLR4 and hypertensive disorder.