Comparative analysis of arterial compliance in mice genetically null for cathepsins K, L, or S.
Comparative analysis of arterial compliance in mice genetically null for cathepsins K, L, or S.
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DOI：
10.1016/j.jbiomech.2022.111266
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发表时间：
2022-08
影响因子：
2.4
通讯作者：
V. Omojola;Zaria Hardnett;Hannah W. Song;Hai Dong;D. J. Alexander;Adeola O Adebayo Michael;R. Gleason;M. Platt
中科院分区：
文献类型：
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作者：
V. Omojola;Zaria Hardnett;Hannah W. Song;Hai Dong;D. J. Alexander;Adeola O Adebayo Michael;R. Gleason;M. Platt
半胱氨酸组织蛋白酶是一种与心血管疾病有关的蛋白酶，可降解细胞外基质（ECM），而ECM的结构和完整性决定了动脉的力学行为。组织蛋白酶基因敲除小鼠模型被用于研究其在心血管疾病中的作用，但组织蛋白酶基因敲除对非动脉粥样硬化动脉力学的影响很少。我们检查了几种组织蛋白酶敲除小鼠系（CatK-/-、CatL-/-Apoe-/-和CatS-/-Apoe-/-）和对照组（C57/B16、载脂蛋白E-/-）的动脉力学。分离三月龄小鼠的颈总动脉，并进行双轴力学测试和开角测试。测得的壁厚和压力-直径曲线被送入一个4纤维本构模型，以评估材料性能的差异。压力-直径数据显示，与CatK−/−、CatS−/−ApoE−/−和ApoE−/−对照相比，CatL−/−ApoE−/−动脉的口径较小，并且在较低压力下的顺应性低于ApoE−/−和CatS−/−ApoE−/−动脉，其中弹性蛋白控制机械反应。与CatL−/−ApoE−/−和CatS−/−ApoE −/−动脉相比，CatK−/−动脉的体内轴向拉伸增加。CatL−/−ApoE−/−动脉的顺应性低于ApoE−/−和CatS−/−ApoE−/−动脉，加压至亚舒张压。4-纤维和统一纤维分布模型能够捕获动脉的非线性力学响应;计算的材料参数表明，与CatL−/−ApoE−/−和CatS−/−ApoE −/−动脉相比，ApoE−/−动脉的轴向参数增加。总而言之，数据表明，强效胶原酶catK的缺失会增加轴向和周向动脉顺应性，而弹性蛋白酶catL的敲除会降低周向动脉顺应性，而弹性蛋白酶catS的敲除对颈动脉力学没有影响。
Cysteine cathepsins are potent proteases implicated in cardiovascular disease for degrading extracellular matrix (ECM) whose structure and integrity determine the mechanical behavior of arteries. Cathepsin knockout mouse models fed atherogenic diets have been used to study their roles in cardiovascular disease, but the impacts of cathepsin knockout on non-atherosclerotic arterial mechanics are scarce. We examine arterial mechanics in several cathepsin knockout mouse lines (CatK−/−, CatL−/−ApoE−/−and CatS−/−ApoE−/−) and controls (C57/Bl6, apolipoprotein E−/−). Common carotid arteries of three month-old mice were isolated and underwent biaxial mechanical testing and opening angle tests. Measured wall thicknesses and pressure-diameter curves were fed into a 4-fiber constitutive model to assess differences in material properties. Pressure-diameter data revealed CatL−/−ApoE−/−arteries were smaller in caliber compared to CatK−/−, CatS−/−ApoE−/−and ApoE−/−controls and were less compliant than ApoE−/−and CatS−/−ApoE−/−arteries at lower pressures, where elastin governs the mechanical response. CatK−/−arteries showed increasedin vivoaxial stretches compared to CatL−/−ApoE−/−and CatS−/−ApoE−/−arteries. CatL−/−ApoE−/−arteries were less compliant than ApoE−/−and CatS−/−ApoE−/−arteries pressurized to sub-diastolic pressures. 4-fiber and unified fiber distribution models were able to capture arteries’ nonlinear mechanical responses; calculated material parameters suggested that ApoE−/−arteries had increased axial parameters compared to CatL−/−ApoE−/−and CatS−/−ApoE−/−arteries. Taken together, the data suggests that loss of the potent collagenase catK increases axial and circumferential arterial compliance, while knockout of the elastase catL decreased circumferential arterial compliance, and knockout of the elastase catS showed no impact on carotid arterial mechanics.