The (pro)renin receptor and the mystic HRP--is there a role in cardiovascular disease?
In 2002, Nguyen et al. cloned the (pro)renin receptor ((P)RR). Two years later, Suzuki, Ichihara and colleagues provided a concept to inhibit the (P)RR through HRP. This decapeptide mimics a sequence of the prorenin prosegment and functions thereby as a decoy peptide. They showed that HRP prevented diabetic nephropathy in rodents and ameliorated renal and cardiac damage in spontaneously hypertensive rats. We tested HRP and the human renin inhibitor aliskiren in transgenic rats overexpressing the human renin and angiotensinogen genes (dTGR). Only aliskiren, but not HRP, was able to ameliorate target organ damage in this model. HRP had also no effect on target organ damage in renovascular hypertensive rats. In vitro studies showed that HRP did not inhibit (pro)renin binding and signaling. More confusing was the fact that HRP bound to cells lacking (P)RR on their surface. We believe that HRP does not act as a competitive antagonist for the (P)RR and promotes its action via an alternative mechanism. Elucidating this mechanism could offer further opportunities, in terms of (pro)renin research.
Maschke
Ulrike
U
Max-Delbruck-Center for Molecular Medicine and Experimental and Clinical Research Center, Berlin-Buch, Germany.
Muller
Dominik N
DN
D000818:Animals; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D006801:Humans; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism; D000093342:Prorenin Receptor
D011956:Receptors, Cell Surface; D025262:Vacuolar Proton-Translocating ATPases; D000093342:Prorenin Receptor