Bicuspid aortic valve aortopathy is characterized by embryonic epithelial to mesenchymal transition and endothelial instability

J Mol Med (Berl). 2023 Jul;101(7):801-811. doi: 10.1007/s00109-023-02316-5. Epub 2023 May 10.


Bicuspid aortic valve (BAV) is the most common congenital heart malformation frequently associated with ascending aortic aneurysm (AscAA). Epithelial to mesenchymal transition (EMT) may play a role in BAV-associated AscAA. The aim of the study was to investigate the type of EMT associated with BAV aortopathy using patients with a tricuspid aortic valve (TAV) as a reference. The state of the endothelium was further evaluated. Aortic biopsies were taken from patients undergoing open-heart surgery. Aortic intima/media miRNA and gene expression was analyzed using Affymetrix human transcriptomic array. Histological staining assessed structure, localization, and protein expression. Migration/proliferation was assessed using ORIS migration assay. We show different EMT types associated with BAV and TAV AscAA. Specifically, in BAV-associated aortopathy, EMT genes related to endocardial cushion formation were enriched. Further, BAV vascular smooth muscle cells were less proliferative and migratory. In contrast, TAV aneurysmal aortas displayed a fibrotic EMT phenotype with medial degenerative insults. Further, non-dilated BAV aortas showed a lower miRNA-200c-associated endothelial basement membrane LAMC1 expression and lower CD31 expression, accompanied by increased endothelial permeability indicated by increased albumin infiltration. Embryonic EMT is a characteristic of BAV aortopathy, associated with endothelial instability and vascular permeability of the non-dilated aortic wall. KEY MESSAGES: Embryonic EMT is a feature of BAV-associated aortopathy. Endothelial integrity is compromised in BAV aortas prior to dilatation. Non-dilated BAV ascending aortas are more permeable than aortas of tricuspid aortic valve patients.

Keywords: Ascending aneurysm; Bicuspid aortic valve; EMT; Endothelial instability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aortic Valve / metabolism
  • Bicuspid Aortic Valve Disease* / complications
  • Bicuspid Aortic Valve Disease* / metabolism
  • Bicuspid Aortic Valve Disease* / pathology
  • Endothelium / metabolism
  • Endothelium / pathology
  • Epithelial-Mesenchymal Transition / genetics
  • Heart Valve Diseases* / complications
  • Heart Valve Diseases* / genetics
  • Heart Valve Diseases* / metabolism
  • Humans
  • MicroRNAs* / metabolism


  • MicroRNAs