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Gene. 2016 Sep 30;590(2):201-9. doi: 10.1016/j.gene.2015.11.047. Epub 2015 Dec 1.

Valsartan ameliorates KIR2.1 in rats with myocardial infarction via the NF-κB-miR-16 pathway.

Author information

1
School of Medicine, Shandong University, Ji'nan, Shandong, China.
2
Department of Cardiology, Qianfoshan Hospital of Shandong Province, Ji'nan, Shandong, China.
3
Department of Cardiology, Qianfoshan Hospital of Shandong Province, Ji'nan, Shandong, China. Electronic address: yansuhua296@163.com.

Abstract

BACKGROUND:

MicroRNAs have an important role in regulating arrhythmogenesis. MicroRNA-16 (miR-16) is predicted to target KCNJ2. The regulation of miR-16 is primarily due to NF-κB. Whether valsartan could downregulate miR-16 via the inhibition of NF-κB after MI and whether miR-16 targets KCNJ2 remain unclear.

METHODS:

MI rats received valsartan or saline for 7days. The protein levels of NF-κB p65, inhibitor κBα (IκBα), and Kir2.1 were detected by Western blot analysis. The mRNA levels of Kir2.1 and miR-16 were examined by quantitative real-time PCR. Whole cell patch-clamp techniques were applied to record IK1.

RESULTS:

MiR-16 expression was higher in the infarct border, and was accompanied by a depressed IK1/KIR2.1 level. Additionally, miR-16 overexpression suppressed KCNJ2/KIR2.1 expression. In contrast, miR-16 inhibition or binding-site mutation enhanced KCNJ2/KIR2.1 expression, establishing KCNJ2 as a miR-16 target. In the MI rats, compared to saline treatment, valsartan reduced NF-κB p65 and miR-16 expression and increased IκBα and Kir2.1 expression. In vitro, angiotensin II increased miR-16 expression and valsartan inhibited it. Overexpressing miR-16 in cells treated with valsartan abrogated its beneficial effect on KCNJ2/Kir2.1. NF-κB activation directly upregulates miR-16 expression.

CONCLUSIONS:

miR-16 controls KCNJ2 expression, and valsartan ameliorates Kir2.1 after MI partly depending on the NF-κB-miR-16 pathway.

KEYWORDS:

Kir2.1; Myocardial infarction; NF-κB; Rats; Valsartan; miR-16

PMID:
26654716
DOI:
10.1016/j.gene.2015.11.047
[Indexed for MEDLINE]

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