Hemodynamic Shear Stresses in Mouse Aortas: Implications for Atherogenesis

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.

[1]  P. Weinberg,et al.  Twenty-fold difference in hemodynamic wall shear stress between murine and human aortas. , 2007, Journal of biomechanics.

[2]  Charles A. Taylor,et al.  Allometric scaling of wall shear stress from mice to humans: quantification using cine phase-contrast MRI and computational fluid dynamics. , 2006, American journal of physiology. Heart and circulatory physiology.

[3]  S. Nie,et al.  Quantitative 3D fluorescence technique for the analysis of en face preparations of arterial walls using quantum dot nanocrystals and two-photon excitation laser scanning microscopy. , 2006, American journal of physiology. Regulatory, integrative and comparative physiology.

[4]  Manu O. Platt,et al.  Bone Morphogenic Protein 4 Produced in Endothelial Cells by Oscillatory Shear Stress Induces Monocyte Adhesion by Stimulating Reactive Oxygen Species Production From a Nox1-Based NADPH Oxidase , 2004, Circulation research.

[5]  W. R. Taylor,et al.  Quantitative microcomputed tomography analysis of collateral vessel development after ischemic injury. , 2004, American journal of physiology. Heart and circulatory physiology.

[6]  C. Ross Ethier,et al.  Effects of Cardiac Motion on Right Coronary Artery Hemodynamics , 2003, Annals of Biomedical Engineering.

[7]  D. Giddens,et al.  Oscillatory shear stress stimulates endothelial production of O2- from p47phox-dependent NAD(P)H oxidases, leading to monocyte adhesion. , 2003, The Journal of biological chemistry.

[8]  Donna A. Williams.  Intact capillaries sensitive to rate, magnitude, and pattern of shear stress stimuli as assessed by hydraulic conductivity (Lp). , 2003, Microvascular research.

[9]  Don P Giddens,et al.  Effects of wall motion and compliance on flow patterns in the ascending aorta. , 2003, Journal of biomechanical engineering.

[10]  Zahi A Fayad,et al.  Atherosclerotic lesions in genetically modified mice quantified in vivo by non-invasive high-resolution magnetic resonance microscopy. , 2002, Atherosclerosis.

[11]  M. Carrier,et al.  Distribution of Lipid Deposits Around Aortic Branches of Mice Lacking LDL Receptors and Apolipoprotein E , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[12]  M. Cybulsky,et al.  Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation. , 1999, Circulation research.

[13]  R. Nerem,et al.  Oscillatory and steady laminar shear stress differentially affect human endothelial redox state: role of a superoxide-producing NADH oxidase. , 1998, Circulation research.

[14]  R. Ross,et al.  Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-deficient mouse. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[15]  R M Nerem,et al.  Oscillatory shear stress stimulates adhesion molecule expression in cultured human endothelium. , 1998, Circulation research.

[16]  J. D. Smith,et al.  Mouse models of atherosclerosis. , 1998, Laboratory animal science.

[17]  A. Gnasso,et al.  In vivo association between low wall shear stress and plaque in subjects with asymmetrical carotid atherosclerosis. , 1997, Stroke.

[18]  M. Endres,et al.  Focal expression of intercellular adhesion molecule-1 in the human carotid bifurcation. , 1997, Stroke.

[19]  P. Davies,et al.  Flow-mediated endothelial mechanotransduction. , 1995, Physiological reviews.

[20]  S Glagov,et al.  Fluid wall shear stress measurements in a model of the human abdominal aorta: oscillatory behavior and relationship to atherosclerosis. , 1994, Atherosclerosis.

[21]  J. Ando,et al.  Wall shear stress rather than shear rate regulates cytoplasmic Ca++ responses to flow in vascular endothelial cells. , 1993, Biochemical and biophysical research communications.

[22]  P. Stone,et al.  Relation of vessel wall shear stress to atherosclerosis progression in human coronary arteries. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[23]  L. Langille,et al.  Remodeling of Developing and Mature Arteries: Endothelium, Smooth Muscle, and Matrix , 1993, Journal of cardiovascular pharmacology.

[24]  D. Ku,et al.  Pulsatile Flow and Atherosclerosis in the Human Carotid Bifurcation: Positive Correlation between Plaque Location and Low and Oscillating Shear Stress , 1985, Arteriosclerosis.

[25]  M. Gimbrone,et al.  Influence of hemodynamic forces on vascular endothelial function. In vitro studies of shear stress and pinocytosis in bovine aortic cells. , 1984, The Journal of clinical investigation.

[26]  C. Zarins,et al.  Carotid Bifurcation Atherosclerosis: Quantitative Correlation of Plaque Localization with Flow Velocity Profiles and Wall Shear Stress , 1983, Circulation research.

[27]  R. Schroter,et al.  Atheroma and arterial wall shear - Observation, correlation and proposal of a shear dependent mass transfer mechanism for atherogenesis , 1971, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[28]  D. L. Fry.  Acute Vascular Endothelial Changes Associated with Increased Blood Velocity Gradients , 1968, Circulation research.