Soluble (pro)renin receptor: a novel ligand for angiotensin II type 1 receptor?

This commentary highlights the study entitled 'Soluble (pro)renin receptor induces endothelial dysfunction and hypertension in mice with diet-induced obesity via activation of angiotensin II type 1 receptor' presented by Fu et al. published in Clinical Science (Clin Sci (Lond) (2021) 135(6), https://doi.org/10.1042/CS20201047). The authors evaluated the role of the soluble (pro)renin receptor (sPRR), a cleavage product of the prorenin receptor (PRR) by the site 1 protease, as a ligand for angiotensin II type 1 receptor (AT1R). They presented for the first time that sPRR directly interacts with AT1R, causing nuclear factor-kappa B activation, inflammation, apoptosis, and endothelial dysfunction in primary human umbilical vein endothelial cells (HUVECs). Furthermore, the interaction between sPRR and AT1R was responsible for endothelial dysfunction and hypertension in diet-induced obesity mice. These results provide a potential mechanism for obesity-induced endothelial dysfunction and hypertension. Thus, the sPRR/AT1R complex may be a novel therapeutic target for cardiovascular diseases associated with endothelial dysfunction.