Patent ID: 11007266

Abstract:
Angiotensin II (AngII) has been strongly implicated in hypertension and its complications. Evidence suggests the mechanisms by which angiotensin II (AngII) elevates blood pressure and enhances cardiovascular remodeling and damage may be distinct. In vascular smooth muscle cells, a metaloproteinase ADAM17 mediates epidermal growth factor receptor (EGER) transactivation, which may be responsible for cardiovascular remodeling but not hypertension induced by AngII. Treatment with a human cross-reactive ADAM17 inhibitory antibody (A9B8) also prevented cardiovascular, remodeling and ER stress but not hypertension in C57Bl/6 mice infused with AngII. In vitro data further supported these findings. In conclusion, vascular ADAM17 mediates AngII-induced cardiovascular remodeling via EGFR activation independent of blood pressure regulation. ADAM17 presents a unique therapeutic target for antibodies such as A9B8 for the prevention of hypertensive complications.