Most ET-1 in the circulation is cleared quickly by ETB receptors in the lungs, kidneys, and liver (38, 39), keeping concentrations low; therefore, higher circulating ET-1 may be reflective of increased local release, as is the case in pathological conditions such as atherosclerosis (40), pulmonary hypertension (41), and heart failure (42). The gene discussed is EDN1; the disease is atherosclerosis.