Thorac Cardiovasc Surg 2025; 73(S 01): S1-S71
DOI: 10.1055/s-0045-1804143
Monday, 17 February
NEUE TECHNOLOGIEN: VON EKZ BIS KI

Distinct Gene Signatures in Aortic Tissue and Aortic Valves with Stenosis and Insufficiency in Patients with Ascending Thoracic Aortic Aneurysm

S. Seeler
1   Department of Cardiovascular Surgery, Institute Insure, German Heart Center Munich, München, Deutschland
,
E. Dzilic
1   Department of Cardiovascular Surgery, Institute Insure, German Heart Center Munich, München, Deutschland
,
F. Wirth
1   Department of Cardiovascular Surgery, Institute Insure, German Heart Center Munich, München, Deutschland
,
K. C. König
1   Department of Cardiovascular Surgery, Institute Insure, German Heart Center Munich, München, Deutschland
,
H. Lahm
1   Department of Cardiovascular Surgery, Institute Insure, German Heart Center Munich, München, Deutschland
,
R. ÖLlinger
3   Department of Medicine II, School of Medicine, Technical University of Munich, Munich, Deutschland
,
R. Rad
3   Department of Medicine II, School of Medicine, Technical University of Munich, Munich, Deutschland
,
T. Trenkwalder
2   TUM University Hospital, Technical University of Munich, Munich, Deutschland
,
S. Doppler
1   Department of Cardiovascular Surgery, Institute Insure, German Heart Center Munich, München, Deutschland
,
M. Krane
1   Department of Cardiovascular Surgery, Institute Insure, German Heart Center Munich, München, Deutschland
,
M. Dreßen
1   Department of Cardiovascular Surgery, Institute Insure, German Heart Center Munich, München, Deutschland
› Author Affiliations

Background: Ascending thoracic aortic aneurysm (ATAA) is characterized by a destabilization and degradation of the medial layer of the aortic wall, harboring the life-threatening risk for aortic rupture. It is known that pathological alterations of the aortic valve (AVa), including AVa stenosis (AS) and AVa insufficiency (AI) that show higher prevalence in patients with bicuspid AVas (BAV), contribute to ATAA development. In the present study, we aim to elucidate the gene expression changes in the aortic wall specific to the respective AVa pathology and evaluate the transcript changes in AVa tissues of ATAA patients.

Methods: Here, we performed 3′-poly(A)-RNA sequencing on human aortic and AVa tissues. Aortic tissue was donated by patients with (n = 14) and without (n = 9) ATAA undergoing cardiac surgery and displaying BAV with AS (n = 13) or AI (n = 10). AVa samples were collected from patients with ATAA and bicuspid (n = 6) or tricuspid (n = 5) as well as AS (n = 6) or AI (n = 5) pathology. After raw data processing, differential expression analysis (DEA), gene ontology, and KEGG pathway analyses were performed.

Results: DEA of aortic tissue from patients with ATAA revealed 130 differentially expressed transcripts, including seven long non-coding RNAs (lncRNAs). The majority of differentially expressed genes (DEGs) were downregulated and were associated with inflammatory responses, immune cell migration, and apoptotic processes. When analyzing the subgroup of patients with AS, we found 40 DEGs in ATAA patients compared with AS patients without ATAA, which were associated with biological processes like muscle tissue development and response to calcium ions. In contrast, for AI patients with ATAA 42 DEGs were discovered, which mainly concerned epithelial cell proliferation and cell–cell adhesion. Thereby, only 13 of these DEGs were shared between AS and AI subgroups. DEA of AVa tissue from ATAA patients with AS compared with AI further revealed 159 differentially regulated transcripts, including three lncRNAs. The DEGs associated with the regulation of ossification, BMP signaling, and extracellular matrix formation.

Conclusion: The present study provides insights into gene expression changes that could not only contribute to further identify mechanisms in the interplay of AVa pathology and the development of ATAA, but also the underlying mechanistic processes of AS and AI in ATAA patients.



Publication History

Article published online:
11 February 2025

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