RRC ID 54473
Author Yoshida A, Kanamori H, Naruse G, Minatoguchi S, Iwasa M, Yamada Y, Mikami A, Kawasaki M, Nishigaki K, Minatoguchi S.
Title (Pro)renin Receptor Blockade Ameliorates Heart Failure Caused by Chronic Kidney Disease.
Journal J Card Fail
Abstract BACKGROUND:The (pro)renin receptor [(P)RR)] is involved in the activation of local renin-angiotensin system and subsequent development of cardiovascular disease. We investigated the therapeutic effect of a (P)RR blocker, handle-region peptide (HRP), on chronic kidney disease (CKD)-associated heart failure.
METHODS AND RESULTS:CKD was induced in C57BL/6J mice by means of five-sixths nephrectomy. Eight weeks later, cardiac dysfunction and cardiac dilatation with hypertension developed. Mice were then assigned to 1 of the 3 following groups: vehicle, low-dose (0.01 mg·kg-1·d-1) HRP, or high-dose (0.3 mg·kg-1·d-1) HRP for 4 weeks. High-dose HRP treatment reversed left ventricular dilation and significantly improved cardiac dysfunction with ameliorated hypertension compared with the vehicle. The hearts with high-dose HRP treatment showed significant attenuation of cardiac fibrosis, cardiomyocyte hypertrophy, macrophage infiltration, and oxidative DNA damage. This treatment decreased the myocardial expressions of angiotensin (Ang) II, Ang II type 1 receptor, transforming growth factor β1, extracellular matrix-related proteins, and lipid peroxidation. Autophagy was activated in the cardiomyocyte from nephrectomized mice, but HRP treatment had no effect on cardiomyocyte autophagy.
CONCLUSIONS:This study indicates that (P)PR blockade is a beneficial strategy by suppressing cardiac fibrosis and hypertrophy to ameliorate heart failure caused by CKD.
Volume 25(4)
Pages 286-300
Published 2019-4-1
DOI 10.1016/j.cardfail.2019.02.009
PII S1071-9164(19)30166-6
PMID 30769036
MeSH Animals Blotting, Western Disease Models, Animal Dose-Response Relationship, Drug Heart Failure / diagnosis Heart Failure / etiology Heart Failure / prevention & control* Immunohistochemistry Male Mice Mice, Inbred C57BL Mice, Transgenic Microscopy, Electron Myocardium / ultrastructure Oligopeptides / administration & dosage* Prorenin Receptor Receptors, Cell Surface / antagonists & inhibitors* Renal Insufficiency, Chronic / complications* Renal Insufficiency, Chronic / drug therapy Renal Insufficiency, Chronic / metabolism
IF 3.967
Times Cited 2
Mice RBRC00806