Despite its vital importance for establishing proper cardiovascular function, the process through which the vasculature develops and matures postnatally remains poorly understood. From a clinical perspective, an ability to mechanistically model the developmental time course in arteries and veins, as well as to predict how various pathologies and therapeutic interventions alter the affected vessels, promises to improve treatment strategies and long-term clinical outcomes, particularly in pediatric patients suffering from congenital heart defects. In the present study, we conducted a multiscale investigation into the postnatal development of the murine thoracic aorta, examining key allometric relations as well as relationships between in vivo mechanical stresses, collagen and elastin expression, and the gradual accumulation of load-bearing constituents within the aortic wall. Our findings suggest that the production of fibrillar collagens in the developing aorta associates strongly with the ratio of circumferential stresses between systole and diastole, hence emphasizing the importance of a pulsatile mechanobiological stimulus. Moreover, rates of collagen turnover and elastic fiber compaction can be inferred directly by synthesizing transcriptional data and quantitative histological measurements of evolving collagen and elastin content. Consistent with previous studies, we also observed that wall shear stresses acting on the aorta are similar at birth and in maturity, supporting the hypothesis that at least some stress targets are established early in development and maintained thereafter, thus providing a possible homeostatic basis to guide future experiments and inform future predictive modeling.

尽管它对于建立适当的心血管功能至关重要，但血管系统在出生后发育和成熟的过程仍然知之甚少。从临床角度来看，机械地模拟动脉和静脉的发育时间过程，以及预测各种病理和治疗干预如何改变受影响血管的能力，有望改善治疗策略和长期临床结果，特别是在儿科患有先天性心脏病的患者。在本研究中，我们对小鼠胸主动脉的出生后发育进行了多尺度研究，检查了关键的异速生长关系以及体内机械应力、胶原蛋白和弹性蛋白表达以及承重成分在胸主动脉内逐渐积累之间的关系。主动脉壁。我们的研究结果表明，发育中的主动脉中纤维状胶原蛋白的产生与收缩期和舒张期之间的周向应力比率密切相关，因此强调了脉动机械生物学刺激的重要性。此外，通过合成转录数据和不断变化的胶原蛋白和弹性蛋白含量的定量组织学测量，可以直接推断胶原蛋白周转率和弹性纤维压缩率。与之前的研究一致，我们还观察到作用于主动脉的壁剪应力在出生时和成熟时是相似的，支持这样的假设：至少有一些应力目标在发育早期建立并在之后维持，从而提供了可能的稳态基础来指导未来的实验并为未来的预测建模提供信息。