The B6D2F1 Strain: A Novel Mouse Model of Human Vascular Aging

Human vascular aging is characterized by increased large elastic artery stiffness and decreased endothelium‐dependent dilation (EDD). Most aging studies in mice utilize the C57BL6 strain, but the availability of older mice of this strain recently was restricted by the National Institute on Aging. Thus, there is need to establish new mouse strains as models of human vascular aging. To determine if the B6D2F1 makes an effective model, 10 young (6–8 mo, Y) and 11 older (29–34 mo, O) male mice were studied. The passive mechanical properties of carotid arteries were assessed in vitro, and the stiffness coefficient was calculated from the stress‐strain relation. Carotid arteries from O mice demonstrated higher relative stiffness compared with Y (7.77 ± 1.34 vs. 4.74 ± 0.73, p=0.036). Moreover, EDD to acetylcholine (ACh) was reduced in isolated carotid and femoral arteries from O vs. Y mice (Carotid: 73.0 ± 5.2 % vs. 96.9 ± 2.0%, p<0.002; Femoral: 86.8 ± 3.0 % vs. 98.6 ± 0.8%, p<0.001). In vivo, the blood pressure lowering effect of systemic infusion of ACh tended to be blunted in O (N=5) compared with Y (N=4) mice (p=0.1). These results indicate that older B6D2F1 mice demonstrate both increased large elastic artery stiffness and endothelial dysfunction. These changes are consistent with those observed in older adult humans, and thus provide rationale for the use of the B6D2F1 mouse as a model of human vascular aging. Work funded by NIA grants: AG006537, AG013038, AG022241.