Identification of a novel flow-mediated gene expression signature in patients with bicuspid aortic valve
2013 (English)In: Journal of Molecular Medicine, ISSN 0946-2716, E-ISSN 1432-1440, Vol. 91, no 1, 129-139 p.Article in journal (Refereed) Published
Rationale: Individuals with bicuspid aortic valve (BAV) are at significantly higher risk of developing serious aortic complications including aortic aneurysm and dissection than individuals with a tricuspid aortic valve (TAV). Studies have indicated an altered aortic blood flow in patients with BAV, however the extent to which altered flow may influence the pathological state of BAV aorta is still unclear.
Objective: To dissect flow-mediated gene expression potentially leading to increased aneurysm susceptibility in patients with BAV.
Methods and Results: A large collection of publically available microarray data sets were screened for consistent co-expression with KLF2, KLF4, TIE1, THBD, and PKD2, five previously well-characterized flow-regulated genes. This identified 122 genes with coexpression probability of >0.5. Of these, 44 genes satisfied two additional filtering criteria in ascending aorta (127 arrays). The criteria were significant correlation with one or more of the 5 query genes (R>0.40) and differential expression between patients with BAV and TAV. No gene fulfilled the criteria in mammary artery (88 arrays). A large proportion of the identified genes were angiogenesis related genes. Further, 55% of the genes differentially expressed between BAV and TAV showed differential expression in disturbed vs. uniform flow pattern regions in rat aorta. Protein expression of ZFP36, PKD2 and GPR116 were analyzed by immunohistochemistry and their association with BAV were further discussed.
Conclusions: With a new strategy to dissect flow-mediated gene expression, we identified novel genes associated with valve morphology. The complex pattern of blood flow, as a consequence of BAV
Place, publisher, year, edition, pages
Springer-Verlag New York, 2013. Vol. 91, no 1, 129-139 p.
Aneurysm, gene expression, aorta, impaired flow, angiogenesis
IdentifiersURN: urn:nbn:se:liu:diva-73956DOI: 10.1007/s00109-012-0942-8ISI: 000313077000013OAI: oai:DiVA.org:liu-73956DiVA: diva2:479274