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PLoS One. 2017 Oct 24;12(10):e0186635. doi: 10.1371/journal.pone.0186635. eCollection 2017.

Zinc-finger protein 418 overexpression protects against cardiac hypertrophy and fibrosis.

Author information

1
Department of Cardiology, the People's Hospital of Three Gorges University/the First People's Hospital of Yichang, Yichang, China.
2
Department of Intensive Care Unit(ICU), the People's Hospital of Three Gorges University/the First People's Hospital of Yichang, Yichang, China.
3
Department of Inspection office, the People's Hospital of Three Gorges University/the First People's Hospital of Yichang, Yichang, China.
4
Department of Cardiology, the First College of Clinical Medical Sciences of Three Gorges University/ Central People's Hospital of Yichang, Yichang, China.
5
Department of Geriatrics, the People's Hospital of Three Gorges University/the First People's Hospital of Yichang, Yichang, China.
6
Department of B ultrasound room, the People's Hospital of Three Gorges University/the First People's Hospital of Yichang, Yichang, China.
7
Institute of Cardiovascular Diseases, China Three Gorges University, Yichang, China.

Abstract

BACKGROUND:

This study aimed to investigated the effect and mechanism of zinc-finger protein 418 (ZNF418) on cardiac hypertrophy caused by aortic banding (AB), phenylephrine (PE) or angiotensin II (Ang II) in vivo and in vitro.

METHODS:

The expression of ZNF418 in hearts of patients with dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM) and AB-induced cardiac hypertrophy mice, as well as in Ang II- or PE-induced hypertrophic primary cardiomyocytes was detected by western blotting. Then, the expression of ZNF418 was up-regulated or down-regulated in AB-induced cardiac hypertrophy mice and Ang II -induced hypertrophic primary cardiomyocytes. The hypertrophic responses and fibrosis were evaluated by echocardiography and histological analysis. The mRNA levels of hypertrophy markers and fibrotic markers were detected by RT-qPCR. Furthermore, the phosphorylation and total levels of c-Jun were measured by western blotting.

RESULTS:

ZNF418 was markedly down-regulated in hearts of cardiac hypertrophy and hypertrophic primary cardiomyocytes. Down-regulated ZNF418 exacerbated the myocyte size and fibrosis, moreover increased the mRNA levels of ANP, BNP, β-MHC, MCIP1.4, collagen 1a, collagen III, MMP-2 and fibronection in hearts of AB-treated ZNF418 knockout mice or Ang II-treated cardiomyocytes with AdshZNF418. Conversely, these hypertrophic responses were reduced in the ZNF418 transgenic (TG) mice treated by AB and the AdZNF418-transfected primary cardiomyocytes treated by Ang II. Additionally, the deficiency of ZNF418 enhanced the phosphorylation level of c-jun, and overexpression of ZNF418 suppressed the phosphorylation level of c-jun in vivo and in vitro.

CONCLUSION:

ZNF418 maybe attenuate hypertrophic responses by inhibiting the activity of c-jun/AP-1.

PMID:
29065170
PMCID:
PMC5655480
DOI:
10.1371/journal.pone.0186635
[Indexed for MEDLINE]
Free PMC Article

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