The possible role of red blood cell microvesicles in atherosclerosis.

The tendency of sickle cells to adhere to the endothelium reflects the surface features not only of the red cells but also of the endothelial cells. Sickle cell disease is a prototype of a condition where the erythrocyte is under stress, ischemic, oxidative, or shear stress, that causes changes in the erythrocyte morphology. This change leads eventually to enhanced erythrocyte-endothelial cell adhesion. Reactive oxygen species generated by cytokine-activated inflammatory cells oxidize lipoproteins such as LDL and lipoprotein(a) within the vessel wall, facilitating uptake of these particles by activated macrophages and smooth muscle cells, with conversion into lipid-laden foam cells. Notably, the membranes of sickle RBCs have undergone excessive cytoskeletal protein thiol oxidation, and sickle RBCs are abnormally prone to vesiculation during mechanical stress in vitro and apparently in vivo. This abnormality was successfully reproduced in normal RBCs by causing stress conditions using PMS-induced stimulation of intracellular superoxide generation, a process similar to that occurring in sickle RBCs. It could be that the generation of reactive oxygen species in atherosclerosis activates red blood cells, and microvesicles of red blood cells are formed, enhancing the activation of the vascular endothelium and leading to vascular inflammation and atherogenesis.