Is aortic wall shear stress affected by aging? An image-based numerical study with two age groups.

The size of the larger arteries increases during the entire life, but not much is known about how the change in size affects the blood flow. This study compares the flow field in a group of young males (N = 10, age = 23.5 ± 1.4), with a group of older males (N = 8, age = 58.0 ± 2.8). Aortic geometries were obtained by magnetic resonance imaging, and the aortic blood flow field was computed using computational fluid dynamics. The aortic wall shear stress was obtained from the computations, and it was concluded that time-averaged wall shear stress decreased with increased age, probably as a consequence of increased aortic diameter and decreased stroke volume, which in turn reduces the shear rates in the aorta. However, the oscillatory shear index, which is a measure of the oscillatory nature of the wall shear stress vector, seemed to be unaffected by aging.

Identification of a novel flow-mediated gene expression signature in patients with bicuspid aortic valve.

Individuals with bicuspid aortic valve (BAV) are at significantly higher risk of developing serious aortic complications than individuals with tricuspid aortic valves (TAV). Studies have indicated an altered aortic blood flow in patients with BAV; however, the extent to which altered flow influences the pathological state of BAV aorta is unclear. In the present study, we dissected flow-mediated aortic gene expression in patients undergoing elective open heart surgery. A large collection of public microarray data sets were firstly screened for consistent co-expression with five well-characterized flow-regulated genes (query genes). Genes with co-expression probability of >0.5 were selected and further analysed in expression profiles (127 arrays) from ascending aorta of BAV and TAV patients. Forty-four genes satisfied two filtering criteria: a significant correlation with one or more of the query genes (R > 0.40) and differential expression between patients with BAV and TAV. No gene fulfilled the criteria in mammary artery (88 arrays), an artery not in direct contact with the valve. Fifty-five percent of the genes significantly altered between BAV and TAV patients showed differential expression between two identified flow regions in the rat aorta. A large proportion of the identified genes were related to angiogenesis and/or wound healing, with pro-angiogenesis genes downregulated and inhibitory genes upregulated in patients with BAV. Moreover, differential expression of ZFP36, GRP116 and PKD2 was confirmed using immunohistochemistry. Implementing a new strategy, we have demonstrated an angiostatic gene expression signature in patients with BAV, indicating impaired wound healing in these patients, potentially involved in BAV-associated aortopathy.

Characterization of shear-sensitive genes in the normal rat aorta identifies Hand2 as a major flow-responsive transcription factor.

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 combine computational fluid dynamic (CFD) simulations with global microarray analysis to study flow-dependent vessel wall biology in the aortic wall under physiological conditions. METHODS AND RESULTS: Male Wistar rats were used. Animal-specific wall shear stress (WSS) magnitude and vector direction were estimated using CFD based on aortic geometry and flow information acquired by magnetic resonance imaging. Two distinct flow pattern regions were identified in the normal rat aortic arch; the distal part of the lesser curvature being exposed to low WSS and a non-uniform vector direction, and a region along the greater curvature being subjected to markedly higher levels of WSS and a uniform vector direction. Microarray analysis identified numerous novel mechanosensitive genes, including Trpc4 and Fgf12, and confirmed well-known ones, e.g. Klf2 and Nrf2. Gene ontology analysis revealed an over-representation of genes involved in transcriptional regulation. The most differentially expressed gene, Hand2, is a transcription factor previously shown to be involved in extracellular matrix remodeling. HAND2 protein was endothelial specific and showed higher expression in the regions exposed to low WSS with disturbed flow. CONCLUSIONS: Microarray analysis validated the CFD-defined WSS regions in the rat aortic arch, and identified numerous novel shear-sensitive genes. Defining the functional importance of these genes in relation to atherosusceptibility may provide important insight into the understanding of vascular pathology.

Evaluation of aortic geometries created by magnetic resonance imaging data in healthy volunteers.

INTRODUCTION: The development of atherosclerotic plaques has been associated with the patterns of wall shear stress (WSS). However, much is still uncertain with the methods used to calculate WSS. Correct vessel geometries are mandatory to get reliable estimations, and the purpose of this study was to evaluate an in vivo method for creating aortic 3D geometry in human based on data from magnetic resonance imaging (MRI) with ultrasound as reference. METHODS: The aortas of ten healthy men, 23·4 ± 1·6 years of age, were examined with a 1·5 T MRI system using a 3D gadolinium-enhanced gradient-echo sequence. Three-dimensional geometries were created using manual segmentation of images. Lumen diameters (LD) were measured in the abdominal aorta (AA) and the thoracic aorta (TA) with non-invasive B-mode ultrasound as a reference. RESULTS: The anteroposterior diameter of the AA was 13·6 ± 1·1 mm for the MRI and 13·8 ± 1·3 mm for the ultrasound (NS). Intraobserver variability (CV) for MRI and ultrasound was <0·92% and <0·40%, respectively. Interobserver variability for MRI and ultrasound was 0·96% and 0·56%, respectively. The diameter of the TA was 19·2 ± 1·4 mm for the MRI, and the intraobserver variability (CV) was <0·78% and interobserver variability (CV) was 0·92%. CONCLUSION: Specific arterial geometries can be constructed with a high degree of accuracy using MRI. This indicates that the MRI geometries may be used to create realistic and correct geometries in the calculation of WSS in the aorta of human.