Abstract
The arterial stiffening is a strong independent predictor of cardiovascular risk and has been used to characterize the biological age of arteries ('arterial age'). Here we revealed that the Fbln5 gene knockout (Fbln5 (-/-) ) significantly increases the arterial stiffening for both male and female mice. We also showed that the arterial stiffening increases with natural aging, but the stiffening effect of Fbln5 (-/-) is much more severe than aging. The arterial stiffening of 20 weeks old mice with Fbln5 (-/-) is much higher than that at 100 weeks in wild-type (Fbln5 (+/+) ) mice, which indicates that 20 weeks mice (equivalent to ∼26 years old humans) with Fbln5 (-/-) have older arteries than 100 weeks wild-type mice (equivalent to ∼77 years humans). Histological microstructure changes of elastic fibers in the arterial tissue elucidate the underlying mechanism of the increase of arterial stiffening due to Fbln5-knockout and aging. These findings provide new insights to reverse 'arterial age' due to abnormal mutations of Fbln5 gene and natural aging. This work is based on a total of 128 biaxial testing samples of mouse arteries and our recently developed unified-fiber-distribution (UFD) model. The UFD model considers the fibers in the arterial tissue as a unified distribution, which is more physically consistent with the real fiber distribution of arterial tissues than the popular fiber-family-based models (e.g., the well-know Gasser-Ogden-Holzapfel [GOH] model) that separate the fiber distribution into several fiber families. Thus, the UFD model achieves better accuracies with less material parameters. To our best knowledge, the UFD model is the only existing accurate model that could capture the property/stiffness differences between different groups of the experimental data discussed here.