Potential role of the (pro)renin receptor in cardiovascular and kidney diseases

Abstract

The discovery of a (pro)renin receptor ((P)RR) and the introduction of renin inhibitors in the clinic has brought prorenin, the inactive proenzyme form of renin, back into the spotlight. The (P)RR binds both renin and its inactive precursor prorenin, and their binding triggers intracellular signaling that up-regulates the expression of profibrotic genes. Furthermore, binding of prorenin unmasks its active site and endows prorenin with angiotensin I-generating activity. Many studies have attempted to establish a link between (P)RR and hypertension, (P)RR and tissue fibrosis associated with hypertension and with diabetic nephropathy. Models of transgenic rats overexpressing (P)RR develop high blood pressure and have glomerulosclerosis, suggesting a link between increased (P)RR and these pathologies, but no definite proof of any role of (P)RR in other models of cardiovascular or renal diseases could be established because of the absence of any specific (P)RR antagonist and of tissue-specific (P)RR null mice. Nevertheless, a study in a large cohort of Japanese men has shown a correlation between a polymorphism in the (P)RR gene and increased ambulatory blood pressure. Finally, a mutation in the (P)RR gene is responsible for mental retardation and epilepsy, indicating that (P)RR is essential during brain development.