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The cardiac (pro)renin receptor is primarily expressed in myocyte transverse tubules and is increased in experimental diabetic cardiomyopathy

Lookup NU author(s): Dr Andrew Advani, Suzanne Advani, Dr Kathryn White

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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 similar to 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). Conclusion 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. J Hypertens 29: 1175-1184 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Publication metadata

Author(s): Connelly KA, Advani A, Kim S, Advani SL, Zhang M, White KE, Kim YM, Parker C, Thai K, Krum H, Kelly DJ, Gilbert RE

Publication type: Article

Publication status: Published

Journal: Journal of Hypertension

Year: 2011

Volume: 29

Issue: 6

Pages: 1175-1184

Print publication date: 01/06/2011

ISSN (print): 0263-6352

ISSN (electronic): 1473-5598

Publisher: Lippincott Williams & Wilkins

URL: http://dx.doi.org/10.1097/HJH.0b013e3283462674

DOI: 10.1097/HJH.0b013e3283462674

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