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

Freiholtz, D.; Bergman, O.; Lång, K.; Poujade, F.A.; Paloschi, V.; Granath, C.; ... ; Björck, H. (2023)

Article / Letter to editor

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 messagesEmbryonic 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.

• Bicuspid aortic valve
• Ascending aneurysm
• EMT
• Endothelial instability

• All authors: Freiholtz, D.; Bergman, O.; Lång, K.; Poujade, F.A.; Paloschi, V.; Granath, C.; Lindeman, J.H.N.; Olsson, C.; Franco-Cereceda, A.; Eriksson, P.; Björck, H.
• Date: 2023-05-10
• Journal: Journal of Molecular Medicine
• Volume: 101
• Issue: 7
• Pages: 801 - 811
• DOI: doi:10.1007/s00109-023-02316-5
• Link: https://link.springer.com/article/10.1007/s00109-023-02316-5