Tamarixetin protects against cardiac hypertrophy via inhibiting NFAT and AKT pathway

Cardiac hypertrophy is a compensatory response in reaction to mechanical load that reduces wall stress by increasing wall thickness. Chronic hypertrophic remodeling involves cardiac dysfunction that will lead to heart failure and ultimately death. Studies have been carried out on cardiac hypertrophy...

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Bibliographic Details
Published in:Journal of molecular histology 2019-08, Vol.50 (4), p.343-354
Main Authors: Fan, Cheng, Li, Yuan, Yang, Hui, Cui, Yuqian, Wang, Hao, Zhou, Heng, Zhang, Jianning, Du, Binfeng, Zhai, Qian, Wu, Dawei, Chen, Xiaomei, Guo, Haipeng
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
AKT protein
Animals
Aorta
Apoptosis
Biomedical and Life Sciences
Biomedicine
Body weight
Cardiomegaly - prevention & control
Cardiomyocytes
Cardiotonic Agents - pharmacology
Cell Biology
Congestive heart failure
Developmental Biology
Disaccharides - pharmacology
Disaccharides - therapeutic use
Fibrosis - metabolism
Hypertrophy
Life Sciences
Mechanical properties
Mice
NF-AT protein
NFATC Transcription Factors - antagonists & inhibitors
NFATC Transcription Factors - metabolism
Nuclear transport
Original Paper
Oxidative stress
Oxidative Stress - drug effects
Phenylephrine
Protective Agents - pharmacology
Proto-Oncogene Proteins c-akt - antagonists & inhibitors
Proto-Oncogene Proteins c-akt - metabolism
Quercetin
Quercetin - analogs & derivatives
Quercetin - pharmacology
Quercetin - therapeutic use
Reactive oxygen species
Signal Transduction - drug effects
Ventricle
Ventricular Remodeling - drug effects
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Summary:Cardiac hypertrophy is a compensatory response in reaction to mechanical load that reduces wall stress by increasing wall thickness. Chronic hypertrophic remodeling involves cardiac dysfunction that will lead to heart failure and ultimately death. Studies have been carried out on cardiac hypertrophy for years, whereas the mechanisms have not been well defined. Tamarixetin (TAM), a natural flavonoid derivative of quercetin, have been demonstrated possessing anti-oxidative and anti-inflammatory effects on multiple diseases. However, little is known about the function of TAM on the development of cardiac hypertrophy. Here, we found TAM could alleviate pressure-overload-induced cardiac hypertrophy in transverse aortic constriction (TAC) mouse model, assessed by ventricular weight/body weight, lung weight/body weight, echocardiographic parameters, as well as myocyte cross-sectional area and the expression of ANP, BNP and Myh7. In vitro, TAM showed a dose dependent inhibitory effect on phenylephrine-induced hypertrophy in H9c2 cardiomyocytes. Furthermore, TAM reversed cardiac remodeling of stress overloaded heart by suppressing apoptosis and the expression of fibrotic-related genes, reduced oxidative stress and ROS production both in vivo and in vitro. In addition, TAM could negatively modulate TAC-induced nuclear translocation of NFAT and the activation of PI3K/AKT signaling pathways. Therefore, these data indicate for the first time that TAM has a protective effect on experimental cardiac hypertrophy and might be a novel candidate for the treatment of cardiac hypertrophy in clinic.
ISSN:1567-2379
1567-2387
DOI:10.1007/s10735-019-09831-1