Differences in Aortic Arch Geometry, Hemodynamics, and Plaque Patterns Between C57BL/6 and 129/SvEv Mice

Abstract

Atherosclerotic plaques are distributed differently in the aortic arches of C57BL/6 (B6) and 129/ SvEv (129) apolipoprotein E (apoE)-deficient mice. It is now recognized that hemodynamic shear stress plays an important role in the localization of atherosclerotic development. Since the blood flow field in the vessel is modulated by the vascular geometry, we quantitatively examined the difference in the aortic arch geometry between the two corresponding wild-type mouse strains. The three-dimensional (3-D) geometry of fourteen murine aortic arches, seven from each strain, was characterized using casts and stereo microscopic imaging. Many geometric features, including aortic arch shape, vessel diameter, and branch locations were significantly different at p<0.05 between the two mouse strains. Based on the geometry of each cast, an average 3-D geometry of the aortic arch for each mouse strain was obtained, and computational fluid dynamic calculations were performed in the two average aortic arches. Lower shear stress was found at the inner curvature of the aortic arch in the 129 strain, corresponding to greater involvement in the corresponding apoE-deficient mice relative to the B6 strain. These results support the notion that heritable features of arterial geometry can contribute to individual differences in local susceptibility to arterial disease.

Relationship between hemodynamics and atherosclerosis in aortic arches of apolipoprotein E-null mice on 129S6/SvEvTac and C57BL/6J genetic backgrounds

“…In agreement with earlier work (11), we find that anatomical parameters of the aortic arch and mean flow velocities at the ascending and descending aorta are different for the 129 and B6 strains of WT mice. Furthermore, as plaques develop in the aortic arch of apoE-null mice, these differences become exaggerated in a strain-dependent manner.…”

“…The lesions at the aortic arch in apoE-null mice on a 129S6/SvEvTac background (129-apoE) develop more rapidly compared to those on a C57BL/6J (B6-apoE) background, in spite of a slower development of lesions at the aortic root. Moreover, the shape of the aortic arch clearly differs in the two strains (10,11). Accordingly, this pair of strains of apoE-null mouse allows us to explore the relationships among atherosclerosis, hemodynamics, and vascular geometry.…”

Evolution and rupture of vulnerable plaques: a review of mechanical effects

“…In a separate study involving mice, scaling was performed by compressing the diastolic portion of the cardiac cycle, but not the systolic, since it was noted that the decreased cardiac output during anesthesia is predominantly due to decreased heart rate rather than stroke volume. 38 However, not all studies have used an anesthetizedto-conscious scaling technique to obtain the inlet boundary conditions. Trachet et al 39 employed an inlet velocity waveform from humans that was scaled in magnitude and time to match mouse physiology.…”

“…In other studies conducted in mice, the outlet boundary conditions were based on a percentage of the flow rate entering the aortic root. 31,[37][38][39] These studies assume that flow division remains constant throughout the pulse. Huo et al 36 used pressure as a boundary condition when studying pulsatile flow through the mouse aortic arch.…”

“…Consequently, the resulting flow in humans is more complex and eventually turbulent 64 (see next section); however, zones of low WSS are located in the same areas of the arterial tree for both the species, a criterion related to plaque-formation site location. To underline the importance of the geometry in the plaque development process, Tomita et al, 74 continuing from the work of Zhu et al, 38 studied the plaque development in ApoE-null mice of different genetic backgrounds (29S6/ SvEvTac and C57BL/6J). They found that the geometric differences (broader inner curvature for the first, and larger vessel diameter for the second) resulted in a huge difference in the size of the developed plaques in the different mouse strains.…”