As preclinical data indicate that endothelial SDC4 knockout results in elevated BP in mice through the decrease of eNOS activity [52], a vicious circle appears possible, in which the elevated circulating SDC4 levels observed in patients with resistant HTN are associated with a decrease in local endothelial SDC4 maintaining the elevated BP in patients with resistant HTN. The gene discussed is SDC4; the disease is hypertensive disorder.