| Title: |
Empagliflozin improves pressure-overload-induced cardiac hypertrophy by inhibiting the canonical Wnt/β-catenin signaling pathway |
| Authors: |
Xun Yuan, Li Pan, Chi Zhang, Qiulian Zhu, Zexin Huang, Yuan Qin, Guiping Zhang, Zhimei Feng, Caixian Yang, Ning Hou |
| Source: |
Frontiers in Pharmacology, Vol 15 (2024) |
| Publisher Information: |
Frontiers Media S.A., 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Therapeutics. Pharmacology |
| Subject Terms: |
empagliflozin, hypertrophy, FZD, Wnt, beta-Catenin, Therapeutics. Pharmacology, RM1-950 |
| More Details: |
BackgroundEmpagliflozin (EMPA) is an SGLT-2 inhibitor that can control hyperglycemia. Clinical trials have indicated its cardio-protective effects against cardiac remodeling in diabetes or non-diabetes patients. However, the underlying molecular mechanisms of EMPA’s cardio-protective effects remain elusive.MethodsWe evaluated whether the EMPA attenuated the pressure-overload-induced cardiac hypertrophy by inhibiting the Wnt/β-catenin pathway. Furthermore, the effects of the EMPA on a mouse model of transverse aortic constriction (TAC) induced cardiac hypertrophy was also evaluated. Mice were administrated with 0.5% CMC-Na as a vehicle or EMPA (10 mg/kg/day, daily, throughout the study) by intragastric gavage.ResultsThe in vivo echocardiography and histologic morphological analyses revealed that EMPA attenuated TAC-induced cardiac hypertrophy. Moreover, it also ameliorated TAC-induced cardiac fibrosis and decreased the cell size of the cardiomyocytes in isolated adult cardiomyocytes. Molecular mechanism analysis revealed that the EMPA reduced the TAC-induced enhanced expression of the Wnt/β-catenin pathway in vivo. For in vitro assessments, isolated neonatal rat cardiomyocytes (NRCMs) were treated with Angiotensin II (AngII) and EMPA; the results showed that in the absence of EMPA, the expression of the Wnt/β-catenin pathway was enhanced. In the trans-genetic heterozygous β-catenin deletion mice, EMPA attenuated TAC-induced cardiac remodeling by reducing the Wnt/β-catenin pathway. In addition, molecular docking analysis indicated that EMPA interacts with FZD4 to inhibit the TAC and AngII induced Wnt/β-catenin pathway in cardiomyocytes.ConclusionOur study illustrated that EMPA might directly interact with FZD4 to inhibit the TAC and AngII-induced activation of the Wnt/β-catenin pathway to attenuate the adverse cardiac remodeling. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1663-9812 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fphar.2024.1499542/full; https://doaj.org/toc/1663-9812 |
| DOI: |
10.3389/fphar.2024.1499542 |
| Access URL: |
https://doaj.org/article/d6daf312b1bf4acb98726c24d9829787 |
| Accession Number: |
edsdoj.6daf312b1bf4acb98726c24d9829787 |
| Database: |
Directory of Open Access Journals |
