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Patients with bicuspid and tricuspid aortic valve exhibit distinct regional microrna signatures in mildly dilated ascending aorta

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Abstract

MicroRNAs are able to modulate gene expression in a range of diseases. We focused on microRNAs as potential contributors to the pathogenesis of ascending aorta (AA) dilatation in patients with stenotic tricuspid (TAV) or bicuspid aortic valve (BAV). Aortic specimens were collected from the ‘concavity’ and the ‘convexity’ of mildly dilated AAs and of normal AAs from heart transplant donors. Aortic RNA was analyzed through PCR arrays, profiling the expression of 84 microRNAs involved in cardiovascular disease. An in silico analysis identified the potential microRNA–mRNA interactions and the enriched KEGG pathways potentially affected by microRNA changes in dilated AAs. Distinct signatures of differentially expressed microRNAs are evident in TAV and BAV patients vs. donors, as well as differences between aortic concavity and convexity in patients only. MicroRNA changes suggest a switch of SMC phenotype, with particular reference to TAV concavity. MicroRNA changes potentially affecting mechanotransduction pathways exhibit a higher prevalence in BAV convexity and in TAV concavity, with particular reference to TGF-β1, Hippo, and PI3K/Akt/FoxO pathways. Actin cytoskeleton emerges as potentially affected by microRNA changes in BAV convexity only. MicroRNAs could play distinct roles in BAV and TAV aortopathy, with possible implications in diagnosis and therapy.

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Acknowledgements

We are grateful to Ms. MR Cipollaro for assistance.

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Authors and Affiliations

  1. Department of Experimental Medical Science, Lund University, Lund, Sweden

    Sebastian Albinsson, Azra Alajbegovic & Katarzyna K. Krawczyk

  2. Department of Cardiothoracic Sciences, Second University of Naples, Naples, Italy

    Alessandro Della Corte, Ciro Bancone & Marisa De Feo

  3. Department of Experimental Medicine, Section of Biotechnology and Molecular Biology, Second University of Naples, Via L De Crecchio, 7, 80138, Naples, Italy

    Umberto Galderisi, Marilena Cipollaro & Amalia Forte

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  1. Sebastian Albinsson
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  2. Alessandro Della Corte
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  8. Marisa De Feo
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  9. Amalia Forte
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Correspondence to Amalia Forte.

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Funding

This study has been funded by the Swedish Heart and Lung Foundation, the Swedish Research Council, The Royal Physiographic Society and The Magnus Bergvall Foundation (SA) and by the Italian Ministry of Health (RF-GR 2009, Protocol Number GR2009-1580434) (ADC). K.K. Krawczyk is funded through the European Union Marie Curie Initial Training Network SMARTER.

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The authors have no conflicts of interest to declare.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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S. Albinsson and A. Della Corte contributed equally to the study.

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Albinsson, S., Della Corte, A., Alajbegovic, A. et al. Patients with bicuspid and tricuspid aortic valve exhibit distinct regional microrna signatures in mildly dilated ascending aorta. Heart Vessels 32, 750–767 (2017). https://doi.org/10.1007/s00380-016-0942-7

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