Developmental origins of mechanical homeostasis in the aorta. Issue 5 (4th January 2021) - Murtada, Sae‐Il
Abstract: Background: 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. Results: 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. Conclusions: 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. Key Findings: We identify separate cell‐ and tissue‐level mechanical homeostatic set‐points in the murine aorta from the pre‐natal period to maturity. The celllevel homeostatic set‐point for the flow‐induced shear stress experienced by endothelial cells is established by postnatal day P2. This early celllevel set‐point is necessary to guide proper aortic development, involving deposition and maturation of extracellular matrix which increasingly stress shields intramural smooth muscle cells to restore homeostasis. As the extracellular matrix matures, tissue‐level set‐points for intramural stress develop which can be used to further assess and model aortic homeostasis after maturity.