Background and Aims: Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by chronic inflammation, high blood pressure, oxidative stress, and progressive loss of cell and organ function with aging. We propose a hypothesis that the development of atherosclerosis is based on oxidative stress of erythrocytes and their senescence.

Methods: Our hypothesis is based on several facts. At the first, it is known that cholesterol content is increased in membrane of senescent erythrocytes. The second, senescent erythrocytes lose their plasticity and ability of deformation, which affects the rheological blood properties, that can injure the vessel wall. The third, macrophages are involved in all stages of atherogenesis. They can undergo polarization by shifting between M1 and M2 functional phenotypes.

Results: It is known that efferocytosis, or ingestion of apoptotic cells, is stimulated by M2 macrophage polarization and macrophage polarization toward the pro-inflammatory M1 macrophage is a major promoter to atheroma formation. It is known that efferocytosis, or ingestion of apoptotic cells, is stimulated by M2 macrophage polarization. A failure of efferocytosis leads to a prolongation of chronic pathology in tissue. In addition, fat-laden macrophages contribute to plague progression by transforming into foam cells in response to excess lipid deposition in arteries. We postulate that the main source of lipid accumulation in foam cells are senescent erythrocytes.

Conclusions: It is necessary to concentrate on the study of the role of senescent erythrocytes in atherogenesis, and to test our hypothesis in animal models. This work is supported by a grant from the Russian Scientific Foundation №17-75-20249