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Transcriptional and post-transcriptional regulation of CCN genes in failing heart

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Abstract

Background

CCN family of proteins has been implicated in various processes in cardiovascular physiology and pathology, including angiogenesis, regeneration and fibrosis. In this study we assessed long term changes of CCN1 and CCN2 gene products abundance in the failing ventricular myocardium.

Methods

Male, 12–14-weeks-old C57BL6/J and C57BL6/J IL−6−/− mice were used. To assess short term changes, a transient reversible ischemia model was utilized. Heart failure was caused by ligation of anterior descending coronary artery. The presence of systolic dysfunction was confirmed by echocardiography and left ventricular ANP RNA expression. Molecular analysis was performed on left ventricular samples from animals sacrificed 12–14 weeks after infarction. Western blotting and QT-PCR were used to investigate abundance of CCN proteins and RNAs, respectively.

Results

Short ischemia resulted in marked increase of CCN1 transcript. However, three months after myocardial infarction (MI), remote myocardium showed a markedly increased expression of CCN1 protein, but not RNA. In the case of CCN2, the RNA was distinctly up-regulated, whereas the protein presented only modest, non-significant increase in failing myocardium. Expression of CCN2 RNA closely correlated with expression of ANP. Long-term telmisartan administration after infarction decreased the expression of CCN1 protein. Interleukin 6 (IL-6) deficiency caused increased CCN2 protein abundance in control animals, but the difference was absent after MI. Infarction did not increase CCN1 protein in the hearts of IL-6 deficient mice.

Conclusion

CCN genes are activated in heart failure. Their regulation is multidimensional both transcriptional and posttranscriptional. The involved pathways include angiotensin II and IL-6.

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Authors and Affiliations

  1. Department of General and Experimental Pathology, Medical University of Białystok, Białystok, Poland

    Tomasz A. Bonda, Sergei Litvinovich, Izabela Bialuk, Andrzej Taranta & Maria M. Winnicka

  2. Department of Invasive Cardiology, Medical University of Białystok, Białystok, Poland

    Marcin Kożuch

  3. Department of Medical Therapy, Grodno State University, Grodno, Belarus

    Sergei Litvinovich

  4. Chair and Department of Cardiology, Medical University of Łodz, Łódź, Poland

    Piotr Lipiec & Ewa Szymczyk

  5. Department of Cardiology, Medical University of Bialystok, Białystok, Poland

    Włodzimierz J. Musiał & Karol A. Kamiński

Authors
  1. Tomasz A. Bonda
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  2. Marcin Kożuch
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  3. Sergei Litvinovich
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  4. Izabela Bialuk
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  5. Andrzej Taranta
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  6. Piotr Lipiec
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  7. Ewa Szymczyk
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  8. Włodzimierz J. Musiał
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  9. Maria M. Winnicka
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  10. Karol A. Kamiński
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Corresponding author

Correspondence to Karol A. Kamiński.

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Bonda, T.A., Kożuch, M., Litvinovich, S. et al. Transcriptional and post-transcriptional regulation of CCN genes in failing heart. Pharmacol. Rep 67, 204–208 (2015). https://doi.org/10.1016/j.pharep.2014.08.019

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  • DOI: https://doi.org/10.1016/j.pharep.2014.08.019

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