In this work we applied a multimodal approach to define the age– and atherosclerosis–related biochemical and functional alterations in red blood cells (RBCs) in ApoE/LDLR^−/− mice. Our results revealed that age–related changes in RBCs, such as decreases in RBC deformability and mean height, were more pronounced in ApoE/LDLR^−/− mice than in age–matched control mice (C57BL/6J). The decreases in phospholipid content and level of lipid unsaturation were accompanied by an increase in cholesterol esters and esterified lipids in RBC membranes in aged C57BL/6J mice. The age–related decrease in the phospholipid content was more pronounced in ApoE/LDLR^−/− mice. In contrast, the increase in the total lipid content in RBC membranes occurred only in ApoE/LDLR^−/− mice with advanced atherosclerosis. The age–related alterations also included a decrease in the ratio of turns to α–helices in the secondary structure of hemoglobin (Hb) inside intact RBCs. On the other hand, an increase in the ratio of unordered conformations to α–helices of Hb was observed only in ApoE/LDLR^−/− mice and occurred already at the age of 5–weeks. This was related to hypercholesterolemia and resulted in an increased oxygen-carrying capacity. In conclusion, progressive mechanical and functional alterations of RBCs in aged ApoE/LDLR^−/− mice were more pronounced than in age–matched C57BL/6J mice. Although, several biochemical changes in RBCs in aged ApoE/LDLR^−/− mice recapitulated age–dependent changes observed in control mice, some biochemical features of RBC membranes attributed to hypercholesterolemia were distinct and could contribute to the accelerated deterioration of RBC function in ApoE/LDLR^−/− mice.

在这项工作中，我们采用了一种多模式方法来确定ApoE / LDLR ^-/-小鼠中与年龄和动脉粥样硬化相关的红细胞（RBC）的生化和功能改变。我们的研究结果表明，与年龄匹配的对照小鼠（C57BL / 6J）相比，ApoE / LDLR ^-/-小鼠与年龄相关的RBC变化，例如RBC变形能力和平均身高的降低更为明显。老年C57BL / 6J小鼠的RBC膜中磷脂含量和脂质不饱和水平的降低伴随着胆固醇酯和酯化脂质的增加。与年龄有关的磷脂含量下降在ApoE / LDLR ^-/-小鼠中更为明显。相反，RBC膜中总脂质含量的增加仅发生在ApoE / LDLR中^-/-患有晚期动脉粥样硬化的小鼠。与年龄有关的变化还包括完整RBC内部血红蛋白（Hb）二级结构的α螺旋匝数比降低。另一方面，仅在ApoE / LDLR ^-/-小鼠中观察到Hb的无序构象与Hbα-螺旋的比率增加，并且已经在5周龄出现。这与高胆固醇血症有关，导致携氧能力增强。总之，与年龄匹配的C57BL / 6J小鼠相比，老年ApoE / LDLR ^-/-小鼠中红细胞的进行性机械和功能改变更为明显。虽然，在老ApoE / LDLR中红细胞的一些生化变化^-/-小鼠概括了在对照小鼠中观察到的年龄依赖性变化，归因于高胆固醇血症的RBC膜的某些生化特征是明显的，并且可能导致ApoE / LDLR ^-/-小鼠RBC功能的加速恶化。