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

Abstract

Objective We investigated the relationships between hemodynamics and differential plaque development at the aortic arch of apolipoprotein E (apoE)-null mice on 129S6/SvEvTac (129) and C57BL/6J (B6) genetic backgrounds. Methods Mean flow velocities at the ascending and descending aorta (mVAA and mVDA) were measured by Doppler ultrasound in wild type and apoE-null male mice at 3 and 9 months of age. Following dissection of the aortic arches, anatomical parameters and plaque areas were evaluated. Results Arch plaques were five times bigger in 129-apoE than in B6-apoE mice at 3 months, and twice as large at 9 months. The geometric differences, namely larger vessel diameter in the B6 strain and broader inner curvature of the aortic arch in the 129 strain, were exaggerated in 9-month-old apoE-null mice. Cardiac output and heart rate under anesthesia were significantly higher in the B6 strain than in the 129 strain. The values of mVAA were similar in the two strains, while mVDA was lower in the 129 strain. However, there was a 129-apoE-specific reduction of flow velocities with age, and both mVAA and mVDA were significantly lower in 129-apoE than in B6-apoE mice at 9 months. The mean relative wall shear stress (rWSS) over the aortic arch in 129-apoE and B6-apoE mice were not different, but animals with lower mean rWSS had larger arch plaques within each strain. Conclusions The plaque formation in the arch of apoE-null mice is accompanied by strain-dependent changes in both arch geometry and hemodynamics. While arch plaque sizes negatively correlate with mean rWSS, additional factors are necessary to account for the strain differences in arch plaque development.

Animal Models of Atherosclerosis

“…It is clear that atherosclerosis is a regional vascular disorder mostly driven by hemodynamics (136) although other developmental factors could also be at play. But there is a necessity for investigators not to generalize about the response too broadly from the study of single vascular sites and at single times.…”

Effects of Shenlian extract on experimental atherosclerosis in ApoE-deficient mice based on ultrasound biomicroscopy

“…Fourth, the information gained by UBM is quite comprehensive. It includes changes in structure, function and hemorheology [30–32]. Finally, UBM approaches can be employed as a real-time imaging tool to study plaque progression.…”

Use of Mouse Models in Atherosclerosis Research

“…A particularly interesting outcome of the comparison of mouse strains involved the study of 129S6/ SvEvTac Apoe −/− strain which exhibited a surprising increase in aortic arch atherosclerosis relative to C57BL/6 Apoe −/− mice. The aortic root in the 129S6/SvEvTac strain is more atheroresistant, but this strain has a sharper angle of curvature for the arch and this appears to induce a difference in shear stress at this vascular site resulting in a hemodynamic environment that promotes lesion initiation and growth [ 72 ]. The development of large panels of recombinant inbred strains offers the potential for the dissection of high-resolution genetic control of various lipid and atherosclerosis phenotypes [ 73 ].…”