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Advanced Study of Aortic Pathology (ASAP)

ABSTRACT: BACKGROUND: The vast majority of thoracic aortic aneurysms (TAAs) are observed either together with a bicuspid aortic valve (BAV), a common congenital disorder, or in idiopathic cases such as patients with a normal tricuspid aortic valve (TAV). The main objective of our study was to identify shared and unique gene expression properties underlying the aortic dilation of BAV and TAV patients. METHODS AND RESULTS: Tissue biopsies for RNA and histological analyses were obtained from aorta of non-dilated (<40mm) and dilated (>45mm) aorta of BAV and TAV patients (in total 131 patients). Additional controls were from mammary artery of the same patients (n=88) and aorta from transplant donors (n=13). Gene expression profiles generated using Affymetrix Exon arrays were analyzed from controls and from aorta intima-media and adventitia of patients (in total 345 samples). 606 genes in aortic intima-media were found to be differentially expressed with dilation. Of these, only few (<4%) were differentially expressed in both BAV and TAV patients. Gene set enrichment analysis identified cell adhesion and extracellular region gene ontology sets as common features of TAA in BAV and TAV patients. The set of immune response genes was observed to be particularly overexpressed in aortic media of dilated TAV samples. CONCLUSION: The divergent gene expression profiles indicate fundamental differences in TAA etiology of BAV and TAV patients. Immune response activation solely in the aorta media of TAV patients suggests that inflammation is a causal factor of TAA in this patient group.

ORGANISM(S): Homo sapiens

PROVIDER: GSE26155 | GEO | 2016/01/15

SECONDARY ACCESSION(S): PRJNA135273

REPOSITORIES: GEO

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Advanced Study of Aortic Pathology (ASAP)

Project description:BACKGROUND: The vast majority of thoracic aortic aneurysms (TAAs) are observed either together with a bicuspid aortic valve (BAV), a common congenital disorder, or in idiopathic cases such as patients with a normal tricuspid aortic valve (TAV). The main objective of our study was to identify shared and unique gene expression properties underlying the aortic dilation of BAV and TAV patients. METHODS AND RESULTS: Tissue biopsies for RNA and histological analyses were obtained from aorta of non-dilated (<40mm) and dilated (>45mm) aorta of BAV and TAV patients (in total 131 patients). Additional controls were from mammary artery of the same patients (n=88) and aorta from transplant donors (n=13). Gene expression profiles generated using Affymetrix Exon arrays were analyzed from controls and from aorta intima-media and adventitia of patients (in total 345 samples). 606 genes in aortic intima-media were found to be differentially expressed with dilation. Of these, only few (<4%) were differentially expressed in both BAV and TAV patients. Gene set enrichment analysis identified cell adhesion and extracellular region gene ontology sets as common features of TAA in BAV and TAV patients. The set of immune response genes was observed to be particularly overexpressed in aortic media of dilated TAV samples. CONCLUSION: The divergent gene expression profiles indicate fundamental differences in TAA etiology of BAV and TAV patients. Immune response activation solely in the aorta media of TAV patients suggests that inflammation is a causal factor of TAA in this patient group. Biobank of patient material. Each tissue sample is from a different patient as indicated by patient ID.

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