Abstract 3764: Aortic Geometry and Plaque Development Affect Hemodynamics in Apoe-Knockout Mice with 129/SvEv and C57BL/6 Genetic Backgrounds
Apoe−/− mice on a 129/SvEv strain background (129Apoe) develop atherosclerosis slower in the aortic roots but faster in the aortic arch than those on a C57BL/6 background (B6Apoe). Since plasma factors circulating in these two regions of aorta are common, we hypothesized that geometric differences affect the hemodynamic parameters and contribute to the different rates of plaque development between the two strains of Apoe−/− mice. We measured velocities of the ascending and the descending aorta (VAA and VDA) by Doppler ultrasound (Vevo 770, VisualSonics) in male wildtype (WT, 9-month-old, n=5) and Apoe−/− mice (3- and 9-month-old, n=4 –7) of the two strains. Aortic arches were dissected, and anatomical parameters and plaque area were measured using images captured under a dissection microscope. VAA was the same in 129WT and B6WT (108.8±6.8 vs 100.6±7.8 cm/s). However, the difference between the VAA and VDA (velocity reduction) was significantly more in 129WT than in B6WT (18.2±3.8 vs 0.3±2.7 cm/s, p<0.05). The VAA in both strains of WT mice was negatively correlated with the luminal area of ascending aorta (r=−0.79, n=10, p<0.05), and the velocity reduction was negatively correlated with the ratio of the luminal areas of ascending and descending aorta (r=−0.66, p<0.05). These data suggest that the continuity equation is applicable to the aorta in the two mouse strains. Our computer simulation based on the geometric features of the aortic arch showed lower levels of shear stress in the inferior curvatures of the arch in 129WT than in B6WT. Consistent with this, the plaque area in the inferior curvatures of the aortic arch was three times greater in old 129Apoe than in old B6Apoe mice (p<0.05). The velocity reduction in old 129Apoe mice was significantly more than in old B6Apoe mice (32.0±3.1 vs 10.6±1.5 cm/s, p<0.05) and in 129WT mice (p<0.05). The velocity reduction in Apoe−/− mice was positively correlated with the plaque area in the inner wall of the aortic arch (r=0.61, n=20, p<0.05) and negatively correlated with the ratio of the lumen area without plaque in ascending and descending aorta (r=−0.70, p<0.05). Thus the hemodynamic parameters are affected by the differences of the aortic geometry in the two strains and exaggerated by the plaques in Apoe−/− mice.