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Unraveling divergent gene expression profiles in bicuspid and tricuspid aortic valve patients with thoracic aortic dilatation: the ASAP study

Journal article
Authors L. Folkersen
D. Wagsater
V. Paloschi
V. Jackson
J. Petrini
S. Kurtovic
S. Maleki
M. J. Eriksson
Kenneth Caidahl
A. Hamsten
J. B. Michel
J. Liska
A. Gabrielsen
A. Franco-Cereceda
P. Eriksson
Published in Molecular medicine
Volume 17
Issue 11-12
Pages 1365-73
ISSN 1076-1551
Publication year 2011
Published at
Pages 1365-73
Language en
Links doi.org/10.2119/molmed.2011.00286
Keywords Aged, Aorta, Thoracic/metabolism/*pathology, Aortic Aneurysm, Thoracic/complications/*genetics/immunology, Biomarkers/metabolism, CD4 Antigens/metabolism, Databases, Genetic, Dilatation, Pathologic, Female, *Gene Expression Profiling, Gene Expression Regulation, Heart Valve Diseases/complications/*genetics/immunology, Humans, Immunity/genetics, Immunohistochemistry, Inflammation/complications/genetics/pathology, Male, Middle Aged, Mitral Valve/metabolism/*pathology, Principal Component Analysis, Reproducibility of Results, Signal Transduction/genetics, Tricuspid Valve/metabolism/*pathology, Tunica Intima/metabolism/pathology, Tunica Media/metabolism/pathology
Subject categories Molecular medicine

Abstract

Thoracic aortic aneurysm (TAA) is a common complication in patients with a bicuspid aortic valve (BAV), the most frequent congenital heart disorder. For unknown reasons TAA occurs at a younger age, with a higher frequency in BAV patients than in patients with a tricuspid aortic valve (TAV), resulting in an increased risk for aortic dissection and rupture. To investigate the increased TAA incidence in BAV patients, we obtained tissue biopsy samples from nondilated and dilated aortas of 131 BAV and TAV patients. Global gene expression profiles were analyzed from controls and from aortic intima-media and adventitia of patients (in total 345 samples). Of the genes found to be differentially expressed with dilation, only a few (<4%) were differentially expressed in both BAV and TAV patients. With the use of gene set enrichment analysis, the cell adhesion and extracellular region gene ontology sets were identified as common features of TAA in both BAV and TAV patients. Immune response genes were observed to be particularly overexpressed in the aortic media of dilated TAV samples. The divergent gene expression profiles indicate that there are fundamental differences in TAA etiology in BAV and TAV patients. Immune response activation solely in the aortic media of TAV patients suggests that inflammation is involved in TAA formation in TAV but not in BAV patients. Conversely, genes were identified that were only differentially expressed with dilation in BAV patients. The result has bearing on future clinical studies in which separate analysis of BAV and TAV patients is recommended.

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