Comparative analysis of endothelial cell and sub-endothelial cell elastic moduli in young and aged mice: Role of CD36

Objective: 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. Approaches and Results: 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 CD36(-/-) mice, 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. Conclusions: 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. (C) 2018 Elsevier Ltd. All rights reserved.