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

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

doi:10.1007/s00335-023-09982-3

journal article

Title:: EGFR and MMP-9 are associated with neointimal hyperplasia in systemic-to-pulmonary shunts in children with complex cyanotic heart disease.
Document type:: Journal Article; Research Support, Non-U.S. Gov't
Author(s):: 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.
Journal title abbreviation:: Mamm Genome
Year:: 2023
Journal volume:: 34
Journal issue:: 2
Pages contribution:: 285-297
Fulltext / DOI:: doi:10.1007/s00335-023-09982-3
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/36867212
Print-ISSN:: 0938-8990
TUM Institution:: Klinik für Chirurgie angeborener Herzfehler und Kinderherzchirurgie (DHM) (Prof. Hörer); Klinik für Herz- und Gefäßchirurgie (DHM) (Prof. Lange)
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Occurrences:

mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Lehr- und Forschungskooperationen mit den Kliniken und Instituten am Deutschen Herzzentrum Klinik für Herz- und Gefäßchirurgie (DHM) (Prof. Krane)2023

mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Lehr- und Forschungskooperationen mit den Kliniken und Instituten am Deutschen Herzzentrum Klinik für Kinderkardiologie und angeborene Herzfehler (DHM) (Prof. Ewert)2023

mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Lehr- und Forschungskooperationen mit den Kliniken und Instituten am Deutschen Herzzentrum Klinik für Chirurgie angeborener Herzfehler und Kinderherzchirurgie (DHM) (Prof. Hörer)2023