title: HRP and prorenin: focus on the (pro)renin receptor and vacuolar H+-ATPase.
abstract: The function of prorenin, the precursor of renin, remained unknown until the discovery of the (pro)renin receptor ((P)RR). (Pro)renin binding to this receptor allows angiotensin generation and induces signaling. Thus, (P)RR blockade will exert effects beyond angiotensin suppression. Recently, the (P)RR has been identified as an accessory protein of the vacuolar-type H+-ATPase, with important roles in Wnt signaling. In addition, transgenic animals overexpressing prorenin display the consequences of angiotensin generation, whereas transgenic animals overexpressing the (P)RR display an angiotensin-independent phenotype. Finally, both beneficial and deleterious effects have been described following treatment with the (P)RR antagonist 'handle region peptide' (HRP), while a (P)RR knockout in cardiomyocytes is lethal. This review highlights the latest findings in the (P)RR area, focusing on cardiovascular and renal pathology. It critically addresses the possibility that (pro)renin acts as an agonist of this receptor in vivo, and discusses the efficacy of HRP. Conclusions are that convincing evidence for (pro)renin-(P)RR interaction in vivo is currently lacking and, thus, that the concept of HRP exerting beneficial effects by blocking such interaction remains to be proven.
authors.affiliation: Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Lu
authors.forename: Alexander H J
authors.initials: AH
authors.lastname: Danser
authors.forename: Marcel E
authors.initials: ME
authors.lastname: Meima
mesh_terms: D000809:Angiotensins / Q000096:biosynthesis*; D000818:Animals; D004330:Drosophila; D051379:Mice; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D014981:Xenopus; D000093342:Prorenin Receptor
chemical_list: D000809:Angiotensins; D009842:Oligopeptides; D011956:Receptors, Cell Surface; D051153:Wnt Proteins; C530358:handle-region peptide, mouse; D012083:Renin; D025262:Vacuolar Proton-Translocating ATPases; D000093342:Prorenin Receptor