Wallace H. Coulter Department of Biomedical Engineering at the Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
The George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
J Biomech. 2022 Oct;143:111266. doi: 10.1016/j.jbiomech.2022.111266. Epub 2022 Aug 27.
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, CatLApoE and CatSApoE) 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 CatLApoE arteries were smaller in caliber compared to CatK, CatSApoE and ApoE controls and were less compliant than ApoE and CatSApoE arteries at lower pressures, where elastin governs the mechanical response. CatK arteries showed increased in vivo axial stretches compared to CatLApoE and CatSApoE arteries. CatLApoE arteries were less compliant than ApoE and CatSApoE 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 CatLApoE and CatSApoE 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.
半胱氨酸组织蛋白酶是参与心血管疾病的强有力的蛋白酶，可降解细胞外基质（ECM），其结构和完整性决定了动脉的机械性能。用动脉粥样硬化饮食喂养的组织蛋白酶敲除小鼠模型已被用于研究其在心血管疾病中的作用，但组织蛋白酶敲除对非动脉粥样硬化动脉力学的影响很少。我们研究了几种组织蛋白酶敲除小鼠系（CatK、CatLApoE 和 CatSApoE）和对照品（C57/Bl6、载脂蛋白 E）的动脉力学。分离 3 月龄小鼠的颈总动脉，进行双向力学测试和开口角度测试。将测量的壁厚和压力-直径曲线输入到 4 纤维本构模型中，以评估材料性能的差异。压力-直径数据显示，与 CatK、CatSApoE 和 ApoE 对照相比，CatLApoE 动脉的口径较小，在较低的压力下，比 ApoE 和 CatSApoE 动脉的顺应性差，在较低的压力下，弹性蛋白控制着机械响应。CatK 动脉的体内轴向拉伸比 CatLApoE 和 CatSApoE 动脉增加。CatLApoE 动脉在低于舒张压的压力下比 ApoE 和 CatSApoE 动脉的顺应性差。4 纤维和统一纤维分布模型能够捕捉动脉的非线性力学响应；计算得到的材料参数表明，与 CatLApoE 和 CatSApoE 动脉相比，ApoE 动脉的轴向参数增加。综上所述，数据表明，强胶原蛋白酶 CatK 的缺失增加了轴向和周向动脉顺应性，而弹性蛋白酶 CatL 的缺失降低了周向动脉顺应性，弹性蛋白酶 CatS 的缺失对颈动脉力学没有影响。
