Le Master Elizabeth, Fancher Ibra S, Lee James, Levitan Irena
Division of Pulmonary and Critical Care, Department of Medicine, University of Illinois at Chicago, United States; Bioengineering, University of Illinois at Chicago, United States.
Division of Pulmonary and Critical Care, Department of Medicine, University of Illinois at Chicago, United States.
J Biomech. 2018 Jul 25;76:263-268. doi: 10.1016/j.jbiomech.2018.06.007. Epub 2018 Jun 18.
To perform comparative analysis of the role of scavenger receptor CD36 on endothelial vs. sub-endothelial elastic modulus (stiffness) in the aortas of young and aged mice.
Elastic moduli of endothelial and sub-endothelial layers of freshly isolated mouse aortas were quantified using atomic force microscopy. In young mice (4-6 months old), we found that while endothelial stiffness is markedly reduced in aortas of CD36mice, as compared to WT controls, no difference between CD36 and WT aortas is observed in the stiffness of the sub-endothelial layer in denuded arteries. Additionally, inhibition of myosin phosphorylation also decreases the elastic modulus in the EC, but not the sub-EC layer in WT mice. Moreover, inhibiting CD36 mediated uptake of oxLDL in intact WT aortas abrogated oxLDL-induced endothelial stiffening. Further analysis of aged mice (22-25 months) revealed that aging resulted not only in significant stiffening of the denuded arteries, as was previously known, but also a comparable increase in the elastic modulus of the endothelial layer. Most significantly, this stiffening in the EC layer is dependent on CD36, whereas the denuded layer is not affected.
Our results show that the role CD36 in stiffening of cellular components of intact aortas is endothelial-specific and that genetic deficiency of CD36 protects against endothelial stiffening in aged mice. Moreover, these data suggest that endothelial stiffness in intact mouse aortas depends more on the expression of CD36 than on the stiffness of the sub-endothelial layer.
对清道夫受体CD36在年轻和老年小鼠主动脉中对内皮与内皮下弹性模量（硬度）的作用进行比较分析。
使用原子力显微镜对新鲜分离的小鼠主动脉内皮和内皮下层的弹性模量进行定量。在年轻小鼠（4 - 6个月大）中，我们发现，与野生型对照相比，CD36基因敲除小鼠主动脉的内皮硬度显著降低，而在去内皮动脉的内皮下层硬度方面，CD36基因敲除小鼠与野生型小鼠之间未观察到差异。此外，抑制肌球蛋白磷酸化也会降低野生型小鼠内皮细胞层的弹性模量，但不会降低内皮下层的弹性模量。而且，抑制完整野生型主动脉中CD36介导的氧化型低密度脂蛋白（oxLDL）摄取可消除oxLDL诱导的内皮细胞硬化。对老年小鼠（22 - 25个月）的进一步分析表明，衰老不仅导致如先前所知的去内皮动脉显著硬化，还导致内皮细胞层弹性模量有类似程度的增加。最显著的是，内皮细胞层的这种硬化依赖于CD36，而去内皮层不受影响。
我们的结果表明，CD36在完整主动脉细胞成分硬化中的作用具有内皮特异性，并且CD36基因缺陷可防止老年小鼠的内皮细胞硬化。此外，这些数据表明完整小鼠主动脉中的内皮硬度更多地取决于CD36的表达，而非内皮下层的硬度。
