Reference - Detail
| 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 |
| Resource | |
| Mice | RBRC00806 |