| Autor: |
Nikiforov NG; Laboratory of Medical Genetics, Institute of Experimental Cardiology, National Medical Research Center of Cardiology, 121552 Moscow, Russia.; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia.; Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia., Zlenko DV; N.N. Semenov Federal Research Center for Chemical Physics RAS, 119991 Moscow, Russia.; Faculty of Biology, M.V. Lomonosov Moscow State University, 119991 Moscow, Russia., Orekhova VA; Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia., Melnichenko AA; Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia., Orekhov AN; Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia.; Laboratory of Infection Pathology and Molecular Microecology, Institute of Human Morphology, 117418 Moscow, Russia. |
| Abstrakt: |
Distribution of different types of atherosclerotic lesions in the arterial wall is not diffuse, but is characterized by mosaicism. The causes of such distribution remain to be established. At the early stages of atherogenesis, low-density lipoprotein (LDL) particles and immune cells penetrate into the intimal layer of the arterial wall through the endothelium. In adult humans, the luminal surface of the arterial wall is a heterogeneous monolayer of cells with varying morphology including typical endothelial cells (ECs) and multinucleated variant endothelial cells (MVECs). We hypothesized that distribution of MVECs in the endothelial monolayer can be related to the distribution pattern of early atherosclerotic lesions. We obtained en face preparations of intact adult (22-59 years old) aortic wall sections that allowed us to study the endothelial monolayer and the subendothelial layer. We compared the distribution of MVECs in the endothelial monolayer with the localization of early atherosclerotic lesions in the subendothelial layer, which were characterized by lipid accumulation and immune cell recruitment. In primary culture, MVECs demonstrated increased phagocytic activity compared to mononuclear ECs. Moreover, we have shown that unaffected aortic intima contained associates formed as a result of aggregation and/or fusion of LDL particles that are non-randomly distributed. This indicated that MVECs may be involved in the accumulation of LDL in the subendothelial layer through increased transcytosis. Interaction of LDL with subendothelial cells of human aorta in primary culture increased their adhesive properties toward circulating immune cells. Study of unaffected aortic intima revealed non-random distribution of leukocytes in the subendothelial layer and increased localization of CD45+ leukocytes in the subendothelial layer adjacent to MVECs. Together, our observations indicate that MVECs may be responsible for the distribution of atherosclerotic lesions in the arterial wall by participating in LDL internalization and immune cell recruitment. |
