Research Papers: Pathology:

Apocynin improving cardiac remodeling in chronic renal failure disease is associated with up-regulation of epoxyeicosatrienoic acids

Kun Zhang _, Yu Liu, Xiaoqiang Liu, Jie Chen, Qingqing Cai, Jingfeng Wang and Hui Huang

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Oncotarget. 2015; 6:24699-24708. https://doi.org/10.18632/oncotarget.5084

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Kun Zhang1,2,*, Yu Liu3,*, Xiaoqiang Liu4,*, Jie Chen2,5, Qingqing Cai6, Jingfeng Wang1,2, Hui Huang1,2

1Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China

2Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou 510120, China

3Department of Cardiology, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530000, China

4Department of Clinical laboratory, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China

5Department of Radiation Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China

6Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Sun Yat-Sen University, Guangzhou 510120, China

*These authors have contributed equally to this work

Correspondence to:

Hui Huang, e-mail: [email protected]

Keywords: Pathology Section, epoxyeicosatrienoic acids, chronic renal failure, cardiac remodeling, apocynin

Received: June 10, 2015     Accepted: August 07, 2015     Published: August 17, 2015


Cardiac remodeling is one of the most common cardiac abnormalities and associated with a high mortality in chronic renal failure (CRF) patients. Apocynin, a nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase inhibitor, has been showed cardio-protective effects. However, whether apocynin can improve cardiac remodeling in CRF and what is the underlying mechanism are unclear. In the present study, we enrolled 94 participants. In addition, we used 5/6 nephrectomized rats to mimic cardiac remodeling in CRF. Serum levels of epoxyeicosatrienoic acids (EETs) and its mainly metabolic enzyme-soluble epoxide hydrolase (sEH) were measured. The results showed that the serum levels of EETs were significantly decreased in renocardiac syndrome participants (P < 0.05). In 5/6 nephrectomized CRF model, the ratio of left ventricular weight / body weight, left ventricular posterior wall thickness, and cardiac interstitial fibrosis were significantly increased while ejection fraction significantly decreased (P < 0.05). All these effects could partly be reversed by apocynin. Meanwhile, we found during the process of cardiac remodeling in CRF, apocynin significantly increased the reduced serum levels of EETs and decreased the mRNA and protein expressions of sEH in the heart (P < 0.05). Our findings indicated that the protective effect of apocynin on cardiac remodeling in CRF was associated with the up-regulation of EETs. EETs may be a new mediator for the injury of kidney-heart interactions.

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