Cells (Jul 2024)

miRNA-Driven Regulation of Endothelial-to-Mesenchymal Transition Differs among Thoracic Aortic Aneurysms

  • Sonia Terriaca,
  • Maria Giovanna Scioli,
  • Fabio Bertoldo,
  • Calogera Pisano,
  • Paolo Nardi,
  • Carmela Rita Balistreri,
  • Daniele Magro,
  • Beatrice Belmonte,
  • Luca Savino,
  • Amedeo Ferlosio,
  • Augusto Orlandi

DOI
https://doi.org/10.3390/cells13151252
Journal volume & issue
Vol. 13, no. 15
p. 1252

Abstract

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Thoracic aortic aneurysms (TAAs) represent a serious health concern, as they are associated with early aortic dissection and rupture. TAA formation is triggered by genetic conditions, in particular Marfan syndrome (MFS) and bicuspid aortic valve (BAV). During the aneurysmatic process, aortic endothelial cells can undergo endothelial-to-mesenchymal transition (End–MT) with consequent phenotypic and functional alterations. We previously documented that MFS TAA is characterized by miR-632–driven End–MT exacerbation, whereas in BAV aortopathy, the occurrence of this process remains still controversial. We investigated the End–MT process and the underlined regulatory mechanisms in BAV, TAV and MFS TAA tissues. Gene expression and immunohistochemical analysis were performed in order to analyze some important miRNAs and genes characterizing End–MT. We documented that BAV endothelium maintains the expression of the endothelial homeostasis markers, such as ERG, CD31 and miR-126-5p, while it shows lower levels of miR-632 and mesenchymal markers compared with MFS. Interestingly, we also found higher levels of miR-632 in MFS patients’ blood. Our findings definitively demonstrate that the End–MT process does not characterize BAV that, among the other TAAs, better maintains the endothelial features. In addition, our results suggest miR-632 as a promising diagnostic/prognostic factor in MFS aortopathy.

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