2. Academic Validation
  3. Tamarixetin protects against cardiac hypertrophy via inhibiting NFAT and AKT pathway

Tamarixetin protects against cardiac hypertrophy via inhibiting NFAT and AKT pathway

  • J Mol Histol. 2019 Aug;50(4):343-354. doi: 10.1007/s10735-019-09831-1.
Cheng Fan 1,  Yuan Li 2 3,  Hui Yang 4,  Yuqian Cui 5,  Hao Wang 2 3,  Heng Zhou 6,  Jianning Zhang 2 3,  Binfeng Du 2 3,  Qian Zhai 2 3,  Dawei Wu 2 3,  Xiaomei Chen 7 8,  Haipeng Guo 9 10
Affiliations

Affiliations

  • 1 Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
  • 2 Department of Critical Care Medicine, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, People's Republic of China.
  • 3 Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, 250012, People's Republic of China.
  • 4 Department of Cardiology, Feicheng Mining Central Hospital, Feicheng, 271600, People's Republic of China.
  • 5 Center for Reproductive Medicine, Qilu Hospital of Shandong University, Jinan, 250012, People's Republic of China.
  • 6 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.
  • 7 Department of Critical Care Medicine, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, People's Republic of China. Chenxm008@126.com.
  • 8 Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, 250012, People's Republic of China. Chenxm008@126.com.
  • 9 Department of Critical Care Medicine, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, People's Republic of China. Haipeng198334@163.com.
  • 10 Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, 250012, People's Republic of China. Haipeng198334@163.com.
PMID: 31111288 DOI: 10.1007/s10735-019-09831-1
Abstract

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.

Keywords

Cardiac hypertrophy; Oxidative stress; Remodeling; Tamarixetin.

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