title: The cardiac (pro)renin receptor is primarily expressed in myocyte transverse tubules and is increased in experimental diabetic cardiomyopathy.
abstract: BACKGROUND
  The pro(renin) receptor is a 350 amino acid transmembrane protein, that on ligand binding, increases the catalytic efficiency of angiotensinogen cleavage by both prorenin and renin, augmenting angiotensin I formation at the cell surface. While implicated in a broad range of diseases, studies to date have focused on the kidney, particularly in the diabetic context. We sought to examine the site-specific expression of the pro(renin) receptor within the heart.
  
  
  METHODS
  Using confocal microscopy, site-specific markers and transmission electron microscopy we assessed the location of the pro(renin) receptor in the heart at both cellular/sub-cellular levels. We assessed pro(renin) receptor expression in the setting of disease and blockade of the renin-angiotensin system, using the TGR[m(Ren2)-27] model of diabetic cardiomyopathy and the direct renin inhibitor, aliskiren.
  
  
  RESULTS
  The pro(renin) receptor was found predominantly at the Z-disc and dyad of cardiac myocytes coinciding closely with the distributions of the vacuolar H⁺-ATPase and ryanodine receptor, known to be located within T-tubules and the sarcoplasmic reticulum's terminal cisternae, respectively. Pro(renin) receptor mRNA/protein abundance were increased ∼3-fold in the hearts of diabetic rats in association with diastolic dysfunction, myocyte hypertrophy and interstitial fibrosis (all P < 0.01). Direct renin inhibition reduced cardiac pro(renin) receptor expression in association with improved cardiac structure/function (all P < 0.05).
  
  
  CONCLUSIONS
  Together, these findings are consistent with the notion that the pro(renin) receptor is a component of the vacuolar H⁺-ATPase, and that like the latter, is increased in the setting of cardiac stress and lowered by the administration of an ostensibly cardioprotective agent.
authors.affiliation: Keenan Research Centre in the Li Ka Shing Knowledge Institute, St. Michael's Hospital and University of Toronto, Toronto, Canada.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Connelly
authors.forename: Andrew
authors.initials: A
authors.lastname: Advani
authors.forename: Sandra
authors.initials: S
authors.lastname: Kim
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Advani
authors.forename: Michael
authors.initials: M
authors.lastname: Zhang
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: White
authors.forename: Young M
authors.initials: YM
authors.lastname: Kim
authors.forename: Colleen
authors.initials: C
authors.lastname: Parker
authors.forename: Kerri
authors.initials: K
authors.lastname: Thai
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Kelly
authors.forename: Richard E
authors.initials: RE
authors.lastname: Gilbert
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D058065:Diabetic Cardiomyopathies / Q000378:metabolism* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D020868:Gene Silencing; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000093342:Prorenin Receptor
chemical_list: D017931:DNA Primers; D011956:Receptors, Cell Surface; D000093342:Prorenin Receptor