| First Author | Dybas J | Year | 2020 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1866 |
| Issue | 12 | Pages | 165972 |
| PubMed ID | 32949768 | Mgi Jnum | J:301007 |
| Mgi Id | MGI:6504170 | Doi | 10.1016/j.bbadis.2020.165972 |
| Citation | Dybas J, et al. (2020) Age-related and atherosclerosis-related erythropathy in ApoE/LDLR(-/-) mice. Biochim Biophys Acta Mol Basis Dis 1866(12):165972 |
| abstractText | 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 alpha-helices in the secondary structure of hemoglobin (Hb) inside intact RBCs. On the other hand, an increase in the ratio of unordered conformations to alpha-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. |
