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Titel:

EGFR and MMP-9 are associated with neointimal hyperplasia in systemic-to-pulmonary shunts in children with complex cyanotic heart disease.

Dokumenttyp:
Journal Article; Research Support, Non-U.S. Gov't
Autor(en):
Kottmann, Philip; Eildermann, Katja; Murthi, Sarala Raj; Cleuziou, Julie; Lemmer, Julia; Vitanova, Keti; von Stumm, Maria; Lehmann, Luisa; Hörer, Jürgen; Ewert, Peter; Sigler, Matthias; Lange, Rüdiger; Lahm, Harald; Dreßen, Martina; Lichtner, Peter; Wolf, Cordula M
Abstract:
Systemic-to-pulmonary shunt malfunction contributes to morbidity in children with complex congenital heart disease after palliative procedure. Neointimal hyperplasia might play a role in the pathogenesis increasing risk for shunt obstruction. The aim was to evaluate the role of epidermal growth factor receptor (EGFR) and matrix-metalloproteinase 9 (MMP-9) in the formation of neointimal within shunts. Immunohistochemistry was performed with anti-EGFR and anti-MMP-9 on shunts removed at follow-up palliative or corrective procedure. Whole-genome single-nucleotide polymorphisms genotyping was performed on DNA extracted from patients´ blood samples and allele frequencies were compared between the group of patients with shunts displaying severe stenosis (≥ 40% of lumen) and the remaining group. Immunohistochemistry detected EGFR and MMP-9 in 24 of 31 shunts, located mainly in the luminal area. Cross-sectional area of EGFR and MMP-9 measured in median 0.19 mm2 (IQR 0.1-0.3 mm2) and 0.04 mm2 (IQR 0.03-0.09 mm2), respectively, and correlated positively with the area of neointimal measured on histology (r = 0.729, p < 0.001 and r = 0.0479, p = 0.018, respectively). There was a trend of inverse correlation between the dose of acetylsalicylic acid and the degree of EGFR, but not MMP-9, expression within neointima. Certain alleles in epidermal growth factor (EGF) and tissue inhibitor of metalloproteinases 1 (TIMP-1) were associated with increased stenosis and neointimal hyperplasia within shunts. EGFR and MMP-9 contribute to neointimal proliferation in SP shunts of children with complex cyanotic heart disease. SP shunts from patients carrying certain risk alleles in the genes encoding for EGF and TIMP-1 displayed increased neointima.
Zeitschriftentitel:
Mamm Genome
Jahr:
2023
Band / Volume:
34
Heft / Issue:
2
Seitenangaben Beitrag:
285-297
Volltext / DOI:
doi:10.1007/s00335-023-09982-3
PubMed:
http://view.ncbi.nlm.nih.gov/pubmed/36867212
Print-ISSN:
0938-8990
TUM Einrichtung:
Klinik für Chirurgie angeborener Herzfehler und Kinderherzchirurgie (DHM) (Prof. Hörer); Klinik für Herz- und Gefäßchirurgie (DHM) (Prof. Lange)
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