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.
[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Geriatr, Wuhan 430022, Hubei, Peoples R China.
[2]Shandong Univ, Qilu Hosp, Dept Crit Care Med, 107 Wenhuaxi Rd, Jinan 250012, Shandong, Peoples R China.
[3]Shandong Univ, Qilu Hosp, Chinese Minist Educ, Key Lab Cardiovasc Remodeling & Funct Res, Jinan 250012, Shandong, Peoples R China.
[4]Shandong Univ, Qilu Hosp, Chinese Minist Hlth, Jinan 250012, Shandong, Peoples R China.
[5]Feicheng Min Cent Hosp, Dept Cardiol, Feicheng 271600, Peoples R China.
[6]Shandong Univ, Qilu Hosp, Ctr Reprod Med, Jinan 250012, Shandong, Peoples R China.
[7]Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430060, Hubei, Peoples R China.
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