MECHANICS AND MODELING OF POSTNATAL ARTERIAL DEVELOPMENT IN WILD-TYPE AND ELASTIN-INSUFFICIENT MICE

摘要

Large arteries in vertebrates serve as elastic reservoirs that store a portion of the blood volume with systole and discharge it during diastole. This function is made possible by the combination of extracellular matrix (ECM) proteins deposited by the smooth muscle cells (SMCs) in the arterial wall. Elastin and collagen expression in mice is first detectable around embryonic day 14 and peaks around postnatal day (P) 14, returning to baseline levels by P30. During this time, pressure and cardiac output increase significantly before leveling off ～P30 [1]. Hence, the protein amounts and consequent mechanical properties of the arterial wall change simultaneously with the applied hemodynamic loads in a complicated and unknown feedback loop. Using elastin-insufficent mice (eln+/-), we can examine how changes in the relative protein amounts alter the mechanics and hemodynamic forces during postnatal development and begin to understand these feedback signals. The relationships between elastin amounts, arterial stiffness and high blood pressure are especially interesting in light of recent studies showing independent correlations between large artery stiffness and hypertension in humans [2]. The mechanical data must be interpreted using microstructurally-based constitutive models to understand how each component contributes to the overall arterial mechanics. These models can assist with rational design of tissue-engineered arteries and disease treatments for ECM-related pathologies, such as Supravalvular Aortic Stenosis (SVAS). In the current study, we evaluate the geometry, mechanics and hemodynamics of wildtype (WT) and elastin-insufficient (eln+/-) aorta from P3 - P60 and fit the data to a microstructurally-based constitutive model to determine the temporal relationships between ECM amounts, mechanical stimuli and cardiovascular function in mice.