Netrin-1 prevents the development of cardiac hypertrophy and heart failure

Wang,Nan; Cao,Yunshan; Zhu,Yan

doi:10.3892/mmr.2016.4755

Netrin-1 prevents the development of cardiac hypertrophy and heart failure

Authors:
- Nan Wang
- Yunshan Cao
- Yan Zhu
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Affiliations: Department of Cardiology, The People's Hospital of Gansu, Lanzhou, Gansu 730000, P.R. China
Published online on: January 11, 2016 https://doi.org/10.3892/mmr.2016.4755
Pages: 2175-2181

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Abstract

The aim of the present study was to examine whether netrin-1 is involved in the development of cardiac hypertrophy, induced by pressure overload. For this investigation, thoracic transverse aortic constriction (TAC) was performed in mice. A total of 18 mice were divided into three groups (n=6 per group): Sham, TAC and TAC + recombinant netrin-1. Neonatal rat cardiomyocytes were stimulated with endothelin-1 (ET-1), and samples were collected to examine the expression levels of netrin‑1 by western blot analysis and the mRNA expression of A‑type natriuretic peptide by reverse transcription‑quantitative polymerase chain reaction. It was found that the expression of netrin‑1 was decreased in the TAC mice and in the neonatal rat cardiomyocytes in response to ET‑1 stimulation. Netrin‑1 eliminated ventricular remodeling, cardiac dysfunction and DNA damage during pressure overload. Furthermore, analysis of the signaling events indicated that netrin‑1‑mediated protection against cardiac hypertrophy was attributed to interruption of the activation of mitogen‑activated protein kinase kinase (MEK) kinase‑1 (K1)‑dependent MEK‑extracellular signal‑regulated protein kinase 1/2 (ERK1/2) and c‑Jun N‑terminal kinase 1/2 (JNK1/2). Therefore, netrin‑1 prevented cardiac hypertrophy and heart failure through the negative regulation of the MEKK1-dependent MEK‑ERK1/2 and JNK1/2 signaling pathways.

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