Journal of molecular and cellular cardiology plus · 2024
Transcriptome analysis of the aortic coarctation area.
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Ellegård Rada, Malm Torsten, Weismann Constance G, Fernlund Eva, Swedish National Biobank for Congenital Heart Disease (SNAB-CHD) consortium, Nordén Björnlert Anneli, Klang Årstrand Hanna, Ellnebo-Svedlund Katarina, Gunnarsson Cecilia
Аннотация
BACKGROUND: Coarctation of the aorta (CoA) is a relatively common congenital heart defect. The underlying causes are not known, but a combination of genetic factors and abnormalities linked to embryonic development is suspected. There are only a few studies of the underlying molecular mechanisms in CoA. The aim of the current study was to expand our understanding of the pathogenesis of CoA by characterizing the transcriptome of the coarctation area.
METHODS: Tissue samples from 21 pediatric patients operated for CoA were dissected into separate biopsies consisting of the localized coarctation itself, proximal/distal tissue and ductus. RNA was sequenced to evaluate gene expression in the different biopsies.
RESULTS: We observed an activation of acute phase response in samples from the localized coarctation compared to samples from distal or proximal tissue. However, we observed even bigger differences for patient age and sex than compared to biopsy location. A cluster of genes located at 1q21, including the S100 gene family, displayed contrasting expression depending on patient sex, and appeared to affect the balance between inflammatory and interferon pathways. Biopsies from patients <3 months old were characterized by a significantly higher fibrotic activity compared to samples from older patients. The ductus tissue was characterized by an upregulation of factors associated with proliferation.
CONCLUSIONS: The ongoing processes in the coarctation area are influenced by the age and sex of the patient, and possibly by differences in etiology between different patients. The impact of patient attributes must be taken into consideration when performing future studies.
METHODS: Tissue samples from 21 pediatric patients operated for CoA were dissected into separate biopsies consisting of the localized coarctation itself, proximal/distal tissue and ductus. RNA was sequenced to evaluate gene expression in the different biopsies.
RESULTS: We observed an activation of acute phase response in samples from the localized coarctation compared to samples from distal or proximal tissue. However, we observed even bigger differences for patient age and sex than compared to biopsy location. A cluster of genes located at 1q21, including the S100 gene family, displayed contrasting expression depending on patient sex, and appeared to affect the balance between inflammatory and interferon pathways. Biopsies from patients <3 months old were characterized by a significantly higher fibrotic activity compared to samples from older patients. The ductus tissue was characterized by an upregulation of factors associated with proliferation.
CONCLUSIONS: The ongoing processes in the coarctation area are influenced by the age and sex of the patient, and possibly by differences in etiology between different patients. The impact of patient attributes must be taken into consideration when performing future studies.