Captopril attenuates TAC-induced heart failure via inhibiting Wnt3a/β-catenin and Jak2/Stat3 pathways
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 s...
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doaj-0359a7f5b14c4cb396254bd9552d7b3c2021-05-20T07:37:18ZengElsevierBiomedicine & Pharmacotherapy0753-33222019-05-01113Captopril attenuates TAC-induced heart failure via inhibiting Wnt3a/β-catenin and Jak2/Stat3 pathwaysYu Zhang0Ling Zhang1Xiaoxue Fan2Weiwei Yang3Boyang Yu4Junping Kou5Fang Li6Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaJiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaJiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaJiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaJiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaCorresponding authors at: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, PR China.; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaCorresponding authors at: Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, PR China.; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaCaptopril (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.http://www.sciencedirect.com/science/article/pii/S0753332218386645CaptoprilTransverse aortic constrictionApoptosisHypertrophyWnt3a/β-cateninJak2/Stat3 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yu Zhang Ling Zhang Xiaoxue Fan Weiwei Yang Boyang Yu Junping Kou Fang Li |
spellingShingle |
Yu Zhang Ling Zhang Xiaoxue Fan Weiwei Yang Boyang Yu Junping Kou Fang Li Captopril attenuates TAC-induced heart failure via inhibiting Wnt3a/β-catenin and Jak2/Stat3 pathways Biomedicine & Pharmacotherapy Captopril Transverse aortic constriction Apoptosis Hypertrophy Wnt3a/β-catenin Jak2/Stat3 |
author_facet |
Yu Zhang Ling Zhang Xiaoxue Fan Weiwei Yang Boyang Yu Junping Kou Fang Li |
author_sort |
Yu Zhang |
title |
Captopril attenuates TAC-induced heart failure via inhibiting Wnt3a/β-catenin and Jak2/Stat3 pathways |
title_short |
Captopril attenuates TAC-induced heart failure via inhibiting Wnt3a/β-catenin and Jak2/Stat3 pathways |
title_full |
Captopril attenuates TAC-induced heart failure via inhibiting Wnt3a/β-catenin and Jak2/Stat3 pathways |
title_fullStr |
Captopril attenuates TAC-induced heart failure via inhibiting Wnt3a/β-catenin and Jak2/Stat3 pathways |
title_full_unstemmed |
Captopril attenuates TAC-induced heart failure via inhibiting Wnt3a/β-catenin and Jak2/Stat3 pathways |
title_sort |
captopril attenuates tac-induced heart failure via inhibiting wnt3a/β-catenin and jak2/stat3 pathways |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2019-05-01 |
description |
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. |
topic |
Captopril Transverse aortic constriction Apoptosis Hypertrophy Wnt3a/β-catenin Jak2/Stat3 |
url |
http://www.sciencedirect.com/science/article/pii/S0753332218386645 |
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