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Regulation mechanism of aquaporin 9 gene on inflammatory response and cardiac function in rats with myocardial infarction through extracellular signal-regulated kinase1/2 pathway

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Abstract

The aim of this study was to investigate the regulation mechanism of aquaporin 9 (AQP9) gene on inflammatory response and cardiac function in rats with myocardial infarction (MI) through extracellular signal-regulated kinase1/2 (ERK1/2) pathway. The constructed rats models of MI were randomly divided into 6 groups: control group (sham operation group, MI modeling sham operation), model group (MI modeling), NC group (MI modeling, tail vein injection of AQP9 negative control sequence vector), AQP9 shRNA group (MI modeling, tail vein injection of AQP9 shRNA plasmid vector), U0126 group (MI modeling, tail vein injection of ERK signaling pathway inhibitor), and AQP9 shRNA + U0126 group. The hemodynamics and cardiac function of rats in each group were detected on the seventh day of modeling. The levels of AQP9 and inflammatory factors [tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10)] in peripheral blood of rats were detected by ELISA method. qRT-PCR and western blot were used to detect the mRNA and protein expression of AQP9, ERK1/2, B-cell lymphoma-2 (Bcl-2), Bcl-associated x (Bax) in the myocardial tissue of rats. TTC and TUNEL staining were used to observe myocardial infarct size and apoptosis of myocardial cells in each group. Compared with control group, the levels of heart rate, left ventricular end-diastolic pressure, TNF-α, and IL-6 were increased in each group of rats with MI (all p < 0.05), while the levels of systolic blood pressure, diastolic blood pressure, mean arterial pressure, left ventricular systolic pressure, and IL-10 were significantly decreased (all p < 0.05). The mRNA and protein expression levels of AQP9, ERK1/2 phosphorylation and Bax were significantly increased, as well as the myocardial infarct size, apoptosis index of myocardial tissue (all p < 0.05), the mRNA and protein expression levels of Bcl-2 were significantly decreased (all p < 0.05). The AQP9 gene knock-down or exogenous administration of the ERK1/2 inhibitor U0126 could improve the above indexes. However, the combination of AQP9 gene knock-down and U0126 showed no further effect. Silencing AQP9 gene can inhibit the activation of ERK1/2 signaling pathway, attenuate the inflammatory response in rats with MI, inhibit apoptosis of myocardial cells, and improve cardiac function.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (81700298).

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Author notes

  1. Xingmei Huang, Xiaobin Yu are co-first authors and have contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, The First Affiliated Hospital of Soochow University, No. 188 Shizi Road, Suzhou, 215006, Jiangsu, China

    Xingmei Huang, Hongxia Li, Lianhua Han & Xiangjun Yang

  2. Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

    Xiaobin Yu

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  1. Xingmei Huang
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  3. Hongxia Li
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  4. Lianhua Han
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  5. Xiangjun Yang
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Correspondence to Xiangjun Yang.

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Ethical approval

This experiment was approved by the Animal Ethics Committee of The First Affiliated Hospital of Soochow University. All animal experiments followed the Declaration of Helsinki. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Huang, X., Yu, X., Li, H. et al. Regulation mechanism of aquaporin 9 gene on inflammatory response and cardiac function in rats with myocardial infarction through extracellular signal-regulated kinase1/2 pathway. Heart Vessels 34, 2041–2051 (2019). https://doi.org/10.1007/s00380-019-01452-8

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