Cardiovascular scaling between humans and mice during postnatal development

Age selection in studies using mouse models is critical to aid translation of findings, but defining equivalent ages between humans and mice is difficult, particularly before maturity, because of tissue-specific variation in developmental timelines across species. For cardiovascular research, such a mapping would provide a framework for the selection of appropriate ages in mouse studies of normal cardiovascular development and (pediatric) cardiovascular disease, including congenital defects. Toward this end, we compiled and mathematically modeled cardiovascular anatomical, functional, and biomechanical results from previous studies of postnatal development to assess whether a cardiovascular-specific age equivalence curve could be derived. For each variable, we determined optimal age scale factors that best align their time courses across humans and mice. The "overall optimal" age scale factor, taken as the mean of the optima across qualitatively similar variables, was 0.69 mouse weeks per human year, although individual optima ranged from 0.4 to 1.3 wk/yr, indicating that no universal scaling can fully align developmental time courses in humans and mice. Applying variable-specific age scale factors may therefore be more appropriate in studies that focus on specific tissues and their loading conditions. Some variables, including heart rate and related clinical metrics (e.g., rate pressure product) as well as aortic wall shear stress, exhibit qualitatively different time courses in humans and mice and cannot be aligned using any scale factor, further highlighting the limitations of this approach. Nevertheless, the optimal age scale factors identified herein can help maximize translational relevance and interpretation of findings from cardiovascular developmental mouse studies.