title: Naringenin attenuates pressure overload-induced cardiac hypertrophy.
abstract: Cardiac hypertrophy is characterized by abnormal enlargement of cardiomyocytes and disproportionate accumulation of extracellular interstitial fibrosis, which are major predictors of the development of coronary artery disease and heart failure. Naringenin is a bitter principle component of grapefruit that has numerous pharmacological effects, including anti-inflammatory, hypolipidemic, antithrombotic and antiatherogenic properties. In order to investigate whether naringenin is able to exert a protective effect against cardiac hypertrophy induced by pressure overload, aortic banding (AB) was performed to induce cardiac hypertrophy in mice, and naringenin was administered for 7 weeks. A total of 60 mice were allocated into four groups: Sham + vehicle, AB + vehicle, sham + naringenin and AB + naringenin. Naringenin treatment attenuated cardiac dysfunction, as indicated by the results of echocardiography and catheter-based measurements at 8 weeks post-surgery. The extent of cardiac hypertrophy was assessed by the heart weight/body weight, heart weight/tibial length and lung weight/body weight ratios, in addition to the cardiomyocyte cross-sectional area and the mRNA expression levels of hypertrophic maker, all of which were mitigated by naringenin administration. Naringenin also inhibited the expression of transforming growth factor-β1, connective tissue growth factor, collagen Iα and collagen IIIα, and attenuated interstitial fibrosis. In addition, naringenin downregulated the activation of the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathways. In conclusion, naringenin attenuated cardiac hypertrophy and interstitial fibrosis, in addition to improving left ventricular function in pressure-overloaded mice. The cardioprotective effect exerted by naringenin may be associated with the inhibition of PI3K/Akt, ERK and JNK signaling pathways.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China ; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China ; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China ; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China ; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China ; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China ; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China ; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Haihan
authors.initials: H
authors.lastname: Liao
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China ; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Zhouyan
authors.initials: Z
authors.lastname: Bian
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China ; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China ; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China ; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China ; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Mengqiao
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China ; Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Qizhu
authors.initials: Q
authors.lastname: Tang
keywords: aortic banding; cardiac hypertrophy; naringenin; pharmacology