Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA.
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut, USA.
Dev Dyn. 2021 May;250(5):629-639. doi: 10.1002/dvdy.283. Epub 2021 Jan 4.
Mechanical homeostasis promotes proper aortic structure and function. Pathological conditions may arise, in part, from compromised or lost homeostasis. There is thus a need to quantify the homeostatic state and when it emerges. Here we quantify changes in mechanical loading, geometry, structure, and function of the murine aorta from the late prenatal period into maturity.
Our data suggest that a homeostatic set-point is established by postnatal day P2 for the flow-induced shear stress experienced by endothelial cells; this value deviates from its set-point from P10 to P21 due to asynchronous changes in mechanical loading (flow, pressure) and geometry (radius, wall thickness), but is restored thereafter consistent with homeostasis. Smooth muscle contractility also decreases during this period of heightened matrix deposition but is also restored in maturity. The pressure-induced mechanical stress experienced by intramural cells initially remains low despite increasing blood pressure, and then increases while extracellular matrix accumulates.
These findings suggest that cell-level mechanical homeostasis emerges soon after birth to allow mechanosensitive cells to guide aortic development, with deposition of matrix after P2 increasingly stress shielding intramural cells. The associated tissue-level set-points that emerge for intramural stress can be used to assess and model the aorta that matures biomechanically by P56.
机械内稳态促进主动脉结构和功能的正常。病理条件的出现部分是由于内稳态的受损或丧失。因此，需要定量评估内稳态及其出现的时间。本研究从胎儿后期到成熟阶段，定量分析了小鼠主动脉的力学加载、几何形状、结构和功能的变化。
我们的数据表明，内皮细胞所经历的血流诱导切应力在出生后第 2 天就达到了内稳态设定点；由于力学加载（流量、压力）和几何形状（半径、壁厚）的非同步变化，从第 10 天到第 21 天，该值偏离设定点，但此后恢复到与内稳态一致。在此期间，基质沉积增加，平滑肌收缩性也降低，但在成熟时也得到恢复。尽管血压升高，但壁内细胞所经历的压力诱导力学应力最初仍然较低，然后随着细胞外基质的积累而增加。
这些发现表明，细胞水平的机械内稳态在出生后不久就出现，以使机械敏感细胞能够指导主动脉的发育，并且在 P2 之后的基质沉积逐渐保护壁内细胞。出现的壁内应力相关组织设定点可用于评估和模拟到第 56 天成熟的生物力学主动脉。
