Female C57BL/6N mice are a viable model of aortic aging in women
Abigail G Longtine 1, Ravinandan Venkatasubramanian 1, Melanie C Zigler 1, Alexandra J Lindquist 1, Sophia A Mahoney 1, Nathan T Greenberg 1, Nicholas S VanDongen 1, Katelyn R Ludwig 1, Kerrie L Moreau 2, Douglas R Seals 1, Zachary S Clayton 1
The aorta stiffens with aging in both men and women, which predicts cardiovascular mortality. Aortic wall structural and extracellular matrix (ECM) remodeling, induced in part by chronic low-grade inflammation, contribute to aortic stiffening. Male mice are an established model of aortic aging. However, there is little information regarding whether female mice are an appropriate model of aortic aging in women, which we aimed to elucidate in the present study. We assessed two strains of mice and found that in C57BL/6N mice, in vivo aortic stiffness (pulse wave velocity, PWV) was higher with aging in both sexes, whereas in B6D2F1 mice, PWV was higher in old versus young male mice, but not in old versus young female mice. Because the age-related stiffening that occurs in men and women was reflected in male and female C57BL/6N mice, we examined the mechanisms of stiffening in this strain. In both sexes, aortic modulus of elasticity (pin myography) was lower in old mice, occurred in conjunction with and was related to higher plasma levels of the elastin-degrading enzyme matrix metalloproteinase-9 (MMP-9), and was accompanied by higher numbers of aortic elastin breaks and higher abundance of adventitial collagen-1. Plasma levels of the inflammatory cytokines interferon-γ, interleukin 6, and monocyte chemoattractant protein-1 were higher in both sexes of old mice. In conclusion, female C57BL/6N mice exhibit aortic stiffening, reduced modulus of elasticity and structural/ECM remodeling, and associated increases in MMP-9 and systemic inflammation with aging, and thus are an appropriate model of aortic aging in women.NEW & NOTEWORTHY Our study demonstrates that with aging, female C57BL/6N mice exhibit higher in vivo aortic stiffness, reduced modulus of elasticity, aortic wall structural and extracellular matrix remodeling, and elevations in systemic inflammation. These changes are largely reflective of those that occur with aging in women. Thus, female C57BL/6N mice are a viable model of human aortic aging and the utility of these animals should be considered in future biomedical investigations.
