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 wall shear stress (WSS) 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 and hemodynamic WSS between the two corresponding wild-type mouse strains. The three-dimensional (3D) geometry of 14 murine aortic arches, seven from each strain, was characterized using casts and stereo microscopic imaging. Based on the geometry of each cast, an average 3D geometry of the aortic arch for each mouse strain was obtained, and computational fluid dynamic calculations were performed in the two average aortic arches. Many geometric features, including aortic arch shape, vessel diameter, and branch locations, were significantly different at p<0.05 between the two mouse strains. 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.

Fig. 1

Different plaque distributions in apoE-deficient C57BL/6 and 129/SvEv mice visualized by Sudan IVB staining.

Fig. 2

(A) The stereo light microscopic imaging system; (B) Top and side views of the calibration device (scale is mm).

Fig. 3

(A) An aortic cast from a C57BL/6 (B6) mouse; (B) The reconstructed 3-D axis of the cast; (C) and (D) Two stereo images of the B6 aortic cast in Fig. 3A; (E) and (F) Computed creaseness (intensity from grey to dark) and the initial plan of the cast axis (white), for the same stereo images; (G) and (H) Final axis projected on the two original images, showing the epipolar lines for the most proximal point.

Fig. 4

(A) The 3-D cast axis transformed to the standard coordinate system defined in the text. The aortic arch extends from the aortic root to the marked dot; (B) The axis of the aortic arch (solid curve) projected on its best-fit plane, and the power function fit to the axis (dashed curve).

Fig. 5

Diameter measurement sites along the aortic arch. The measurements at the four distal sites are only used for computational fluid dynamics.

Fig. 6

Comparison of the average shapes of the B6 (solid curve) and 129 (dashed curve) aortic arches in their respective best-fit plane. The corresponding ±1 SD envelopes are shown in the same line styles in grey. The two aortic axes are aligned at the aortic root along each vessel’s tangent direction at the root. On each aortic axis, the large dot represents the symmetry point of the aortic arch as defined in Materials and Methods, and the three small dots denote the average locations of the right innominate, common carotid and subclavian ostia.

Fig. 7

Time averaged wall shear stress magnitude in the aortic arches of B6 (left) and 129 (right) mice.

Fig. 8

Wall shear stress profile along the inner curvature of the aortic arch of B6 and 129 mice. The dots mark the ostia of the three branches off the arch.