Hemodynamic Shear Stresses in Mouse Aortas

Abstract

Objective-The hemodynamic environment is a determinant of susceptibility to atherosclerosis in the vasculature.Although mouse models are commonly used in atherosclerosis studies, little is known about local variations in wall shear stress (WSS) in the mouse and whether the levels of WSS are comparable to those in humans. The objective of this study was to determine WSS values in the mouse aorta and to relate these to expression of gene products associated with atherosclerosis. Methods and Results-Using micro-CT and ultrasound methodologies we developed a computational fluid dynamics model of the mouse aorta and found values of WSS to be much larger than those for humans. We also used a quantum dot-based approach to study vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression on the aortic intima and demonstrated that increased expression for these molecules occurs where WSS was relatively low for the mouse. Conclusions-Despite large differences in WSS in the two species, the spatial distributions of atherogenic molecules in the mouse aorta are similar to atherosclerotic plaque localization found in human aortas. These results suggest that relative differences in WSS or in the direction of WSS, as opposed to the absolute magnitude, may be relevant determinants of flow-mediated inflammatory responses. and LDL receptor Ϫ/Ϫ mouse lines, have led to an increasing use of the mouse as a model for atherosclerosis. 4,5 However, to relate murine studies to human disease, it is necessary to characterize the hemodynamic patterns found in the mouse and to describe differences and similarities between the two See cover species. Given differences in size, heart rate, and ejection fraction, it is expected that the mouse model does not "scale up" to the human and that the levels and distribution of WSS could be quite different. Consequently, we conducted computational hemodynamic investigations in the mouse aorta as a step toward understanding the environment within which atherosclerosis develops in this animal model. In addition, we examined the spatial distribution of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the mouse aorta. Through this approach, we were able to compute the temporal and spatial distributions of WSS in the mouse aorta and relate these findings to local expression of prototypical proatherogenic proteins. Materials and Methods Geometry Data Acquisition of the Mouse AortaFour animals from a group of twelve-week-old wild-type mice (C57 Bl/6) purchased from the Jackson Laboratory (Bar Harbor, Me) were scanned using micro CT to obtain images of the thoracic aorta. The animals were housed and cared for according to the guidelines proposed by the National Institutes of Health (NIH) for the care and use of experimental animals. After CO 2 euthanasia, the abdominal cavity was dissected to cannulate the abdominal aorta, but the thoracic cavity was left unopened to prevent anatomic distortion of the vasculature. The aorta was then pressure-per...

The influence of anesthesia and fluid–structure interaction on simulated shear stress patterns in the carotid bifurcation of mice

“…Many authors have tried to link local disease patterns to focal zones of locally disturbed shear stress using rigid-walled models of either the aortic arch (Assemat et al, 2014;Feintuch et al, 2007;Suo et al, 2007;Yap et al, 2014), the abdominal aorta (Ford et al, 2011;Greve et al, 2006;Trachet et al, 2011b;Willett et al, 2010) or both (Hoi et al, 2011;Huo et al, 2008;Van Doormaal et al, 2014). The findings of publications that focused on regular WSS patterns (Feintuch et al, 2007;Greve et al, 2006;Huo et al, 2008;Suo et al, 2007;Willett et al, 2010;Yap et al, 2014) are not affected much by our results. However, some findings of publications that focused on the oscillatory patterns of WSS (Assemat et al, 2014;Ford et al, 2011;Hoi et al, 2011;Trachet et al, 2011b;Van Doormaal et al, 2014) might need to be re-interpreted.…”

“…In order to get access to the pre-disease geometry, the authors virtually removed the plaque from the model. Other studies linked wall shear metrics from transient CFD with plaque progression markers such as presence of fat in the wall (Suo et al, 2007) or the expression of VCAM-1 (Hoi et al, 2011). In these studies, the CFD simulations were performed in another group of animals than the group that was used to determine the progression marker(s).…”

Influence of Differential Calcification in the Descending Thoracic Aorta on Aortic Pulse Pressure

“…Multiple mechanisms have been proposed, including altered low-density-lipoprotein cholesterol transportation 20,21 and increased turbulence and wall shear stress, especially in the location of the descending aorta, which has many more branches than the other segments. [22][23][24] For instance, the ascending aorta only has two branches (right and left coronary artery), and the arch has three branches (brachiocephalic, right subclavian, right common carotid). However, the descending aorta has multiple branches, including 11 pairs of posterior intercostal arteries and multiple arteries originating anteriorly, including bronchial, mediastinal, esophageal and pericardial branches as well as superior phrenic arteries.…”

‘Go with the flow ’: A review of methods and advancements in blood flow imaging

“…Reported studies for the use of micro-CT include the assessment of induced or implanted disease models [251,252]; screening for anatomical abnormalities and/or changes in live animals [253]; assessing angiogenesis during fracture healing [254]; in morphological studies, for example, the rodent renal vasculature [255,256]; and the assessment of cancer staging for predictions of metastatic relapse [257]. Micro-CT has also branched into the realm of fluid dynamic simulations in, for instance, the mouse aorta [258,259] and assessment of coronary artery disease [260]. Although in vivo micro-CT imaging is still in its infancy, the possible implications and applications of its use in biomedical research is potentially far-reaching.…”