Captopril attenuates TAC-induced heart failure via inhibiting Wnt3a/β-catenin and Jak2/Stat3 pathways.

Abstract

Captopril (Cap) as angiotensin-converting enzyme inhibitor (ACEi) is commonly used to treat hypertension and some types of congestive heart failure. However, few studies reported on whether Cap exerts a protective effect on myocardial apoptosis induced by transverse aortic constriction (TAC). This study aimed at investigating the possible mechanism of Cap on myocardial apoptosis induced by pressure overload. Results showed that Cap significantly decreased heart-to-body weight ratios (HBWR). Cap markedly improved cardiac function, and reduced inner diameter of ascending aorta (Asc Ao) in TAC mice as shown by echocardiography. Enzyme-linked immunosorbent assay (ELISA) results demonstrated that Cap treatment also markedly decreased the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP), atrial natriuretic peptide (ANP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Cardiac pathological changes and fibrosis have been improved after Cap treatment as shown by hematoxylin-eosin (H&E) staining and Masson's trichrome staining. Moreover, Terminal deoxynucleotidyl transferase-mediated dexoxyuridine triphosphate nick-end labeling (TUNEL) staining result indicated Cap treatment also significantly inhibited cardiac apoptosis. Western Blot results showed that Cap obviously decreased the expression of cleaved capase-3, Bax, phosphorylated Jak2 (p-Jak2), phosphorylated Stat3 (p-Stat3), Wnt3a and β-catenin proteins, as well as increased Bcl-2 expression. In conclusion, Cap showed a protective effect on TAC-induced cardiac apoptosis, which could be attributed to the inhibition of Wnt3a/β-catenin signaling pathway. Cap also attenuated myocardial hypertrophy induced by TAC via suppression of Jak2/Stat3 pathway.

• Authors: Yu Zhang, Ling Zhang, Xiaoxue Fan, Weiwei Yang, Boyang Yu, Junping Kou, Fang Li
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 113 Pg. 108780 (May 2019) ISSN: 1950-6007 [Electronic] France
• PMID: 30889487 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• STAT3 Transcription Factor
• Stat3 protein, mouse
• Wnt3A Protein
• Wnt3a protein, mouse
• beta Catenin
• Captopril
• Jak2 protein, mouse
• Janus Kinase 2

Topics

• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Aorta (drug effects, pathology)
• Apoptosis (drug effects)
• Blotting, Western
• Captopril (pharmacology)
• Enzyme-Linked Immunosorbent Assay
• Heart Failure (prevention & control)
• In Situ Nick-End Labeling
• Janus Kinase 2 (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Myocardium (pathology)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)
• Wnt3A Protein (metabolism)
• beta Catenin (metabolism)