Developmental and Structural Alterations at the Ductus–Aortic Isthmus Interface in Infantile Coarctation of the Aorta: A Biological Basis for Persistent Vascular Disease Beyond Anatomical Repair

Robl IG, Cesnjevar R, Ekici AB, Uebe S, Johann PD, Ramirez MDH, Fincke VE, Fahlbusch FB, Moosmann J (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Journal of Clinical Medicine MDPI

Book Volume: 15

Article Number: 5214

Journal Issue: 13

DOI: 10.3390/jcm15135214

Abstract

Background: Coarctation of the aorta (CoA) is a congenital narrowing of the aortic isthmus near the ductus arteriosus or ligamentum arteriosum. Despite successful anatomical repair, patients remain at risk of recoarctation, arterial hypertension, and diffuse aortopathy, suggesting intrinsic vessel-wall abnormalities beyond localized obstruction. The developmental and molecular basis of these persistent vascular features remains incompletely understood. Methods: Human aortic tissue samples were obtained from 8 male infants with CoA and 6 age- and sex-matched controls aged <1 year. Total RNA was isolated, and gene expression profiling was performed using whole human genome oligo microarrays (Agilent). Differentially expressed transcripts were subjected to pathway, network, and upstream regulator analyses using Ingenuity Pathway Analysis (IPA, Qiagen). Selected candidate genes were evaluated by RT-qPCR in independent verification sets. Results: Transcriptomic profiling identified 402 analysis-ready transcripts distinguishing CoA from control tissue. Exploratory pathway analyses suggested extracellular matrix remodeling characterized by collagen turnover, integrin-mediated cell–matrix interactions, wound-healing signaling, and fibrosis-associated programs. In addition, enrichment analyses identified developmental annotations involving retinoic acid (RA)/RAR/RXR signaling, HOX-associated developmental programs, and a shared HOX/MEIS-associated signature. Network and upstream regulator analyses further suggested associations with cytoskeletal, muscle-associated, and epigenetic regulatory pathways, including KAT6A, KAT6B, retinoic acid/RAR/RXR signaling, DNMT3B, KMT2A, and ARID1A. RT-qPCR independently confirmed increased expression of EDN1, AGTR2, IRS4, and TFAP2B. Conclusions: Infantile CoA tissue exhibited molecular signatures consistent with vessel-wall remodeling accompanied by developmental, vascular signaling, and smooth muscle/cytoskeletal regulatory programs. These findings support the hypothesis that developmental patterning signals and postnatal extracellular matrix remodeling coexist within CoA tissue and may contribute to persistent vascular abnormalities beyond anatomical repair. Given the exploratory nature of the study, these observations should be considered hypothesis-generating and require validation in independent cohorts.

Authors with CRIS profile

Robert Cesnjevar Professur für Herzchirurgie mit dem Schwerpunkt Kinderherzchirurgie Arif Bülent Ekici Institute of Human Genetics Steffen Uebe Institute of Human Genetics

Involved external institutions

Universität Augsburg DE Germany (DE) Bayerisches Zentrum für Krebsforschung (BZKF) DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE)

How to cite

APA:

Robl, I.G., Cesnjevar, R., Ekici, A.B., Uebe, S., Johann, P.D., Ramirez, M.D.H.,... Moosmann, J. (2026). Developmental and Structural Alterations at the Ductus–Aortic Isthmus Interface in Infantile Coarctation of the Aorta: A Biological Basis for Persistent Vascular Disease Beyond Anatomical Repair. Journal of Clinical Medicine, 15(13). https://doi.org/10.3390/jcm15135214

MLA:

Robl, Isabell G., et al. "Developmental and Structural Alterations at the Ductus–Aortic Isthmus Interface in Infantile Coarctation of the Aorta: A Biological Basis for Persistent Vascular Disease Beyond Anatomical Repair." Journal of Clinical Medicine 15.13 (2026).

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