Department of Neurochemistry, Division of Basic and Applied Neurobiology, Serbsky Federal Medical Research Center of Psychiatry and Narcology, Moscow, Russia.
Federal Scientific Clinical Center for Resuscitation and Rehabilitation, Moscow, Russia.
J Cell Mol Med. 2018 Mar;22(3):1366-1382. doi: 10.1111/jcmm.13462. Epub 2018 Jan 24.
Monocytosis and neutrophilia are frequent events in atherosclerosis. These phenomena arise from the increased proliferation of hematopoietic stem and multipotential progenitor cells (HSPCs) and HSPC mobilization from the bone marrow to other immune organs and circulation. High cholesterol and inflammatory signals promote HSPC proliferation and preferential differentiation to the myeloid precursors (i.e., myelopoiesis) that than give rise to pro-inflammatory immune cells. These cells accumulate in the plaques thereby enhancing vascular inflammation and contributing to further lesion progression. Studies in animal models of atherosclerosis showed that manipulation with HSPC proliferation and differentiation through the activation of LXR-dependent mechanisms and restoration of cholesterol efflux may have a significant therapeutic potential.
单核细胞增多症和中性粒细胞增多症是动脉粥样硬化的常见事件。这些现象源于造血干细胞和多能祖细胞(HSPC)的增殖增加,以及 HSPC 从骨髓动员到其他免疫器官和循环中。高胆固醇和炎症信号促进 HSPC 增殖,并优先分化为髓系前体(即髓样发生),进而产生促炎免疫细胞。这些细胞在斑块中积累,从而增强血管炎症,并促进进一步的病变进展。动脉粥样硬化动物模型的研究表明,通过激活 LXR 依赖性机制和胆固醇外排的恢复来操纵 HSPC 的增殖和分化可能具有重要的治疗潜力。