Characterization of Shear-Sensitive Genes in the NormalRat Aorta Identifies Hand2 as a Major Flow-ResponsiveTranscription Factor
2012 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 7, no 12Article in journal (Refereed) Published
Objective: Shear forces play a key role in the maintenance of vessel wall integrity. Current understanding regarding shear-dependent gene expression is mainly based on in vitro or in vivo observations with experimentally deranged shear, hence reflecting acute molecular events in relation to flow. Our objective was to determine wall shear stress (WSS) in the rat aorta and study flow-dependent vessel wall biology under physiological conditions.
Methods and Results: Animal-specific aortic WSS magnitude and vector direction were estimated using computational fluid dynamic simulation based on aortic geometry and flow information acquired by MRI. Two distinct flow pattern regions were identified in the normal rat aorta; the distal part of the inner curvature being exposed to low WSS and a non-uniform vector direction, and a region along the outer curvature being subjected to markedly higher levels of WSS and a uniform vector direction. Microarray analysis revealed a strong differential expression between the flow regions, particularly associated with transcriptional regulation. In particular, several genes related to Ca2+-signalling, inflammation, proliferation and oxidative stress were among the most highly differentially expressed.
Conclusions: Microarray analysis validated the CFD-defined WSS regions in the rat aorta, and several novel flow-dependent genes were identified. The importance of these genes in relation to atherosusceptibility needs further investigation.
Place, publisher, year, edition, pages
2012. Vol. 7, no 12
Aorta, wall shear stress, magnetic resonance imaging, computational fluid dynamics, gene expression
Physiology Fluid Mechanics and Acoustics
IdentifiersURN: urn:nbn:se:liu:diva-73954DOI: 10.1371/journal.pone.0052227ISI: 000312794500119OAI: oai:DiVA.org:liu-73954DiVA: diva2:479263