Novikova Olga A, Laktionov Pavel P, Karpenko Andrey A
1 Department of Vascular and Hybrid Surgery, National Medical Research Institute Academician E.N. Meshalkin National Medical Research Center, Ministry of Health of Russian Federation, Novosibirsk, Russian Federation.
2 Laboratory of Molecular Medicine, SB RAS Institute of Chemical Biology and Fundamental Medicine; E.N. Meshalkin National Medical Research Center, Ministry of Health of Russian Federation, Novosibirsk, Russian Federation.
Vascular. 2019 Feb;27(1):98-109. doi: 10.1177/1708538118796063. Epub 2018 Aug 29.
This paper describes and analyzes the cellular and molecular mechanisms underlying atherosclerosis development. In particular, the roles of monocytes/macrophages, smooth muscle cells, and vascular endothelium in the formation of stable/unstable atheromatous plaques, and the contributions of some processes to atheroma formation.
In this study we analyzed endothelium: function, dysfunction, and involvement into atherogenesis; cell proteins mediating mechanotransduction; proatherogenic role of monocytes; the role of macrophages in the development of unstable atheromatous plaques and smooth muscle cell origin in atherosclerosis. Smooth muscle cell phenotypic switching; their functioning; the ability to retain cholesterol and lipoproteins as well as secretion of pro- and anti-inflammatory molecules and extracellular matrix proteins, their response to extracellular stimuli secreted by other cells, and the effect of smooth muscle cells on the cells surrounding atheromatous plaques are fundamentally important for the insight into atherosclerosis molecular basis.
Atheromatous plaque transcriptome studies will be helpful in the identification of the key genes involved in atheroma transformation and development as well as discovery of the new targets for diagnosis and therapy.
本文描述并分析了动脉粥样硬化发展的细胞和分子机制。特别是,单核细胞/巨噬细胞、平滑肌细胞和血管内皮在稳定/不稳定动脉粥样斑块形成中的作用,以及某些过程对动脉粥样硬化形成的贡献。
在本研究中,我们分析了内皮功能、功能障碍及在动脉粥样硬化发生中的作用;介导机械转导的细胞蛋白;单核细胞的促动脉粥样硬化作用;巨噬细胞在不稳定动脉粥样斑块发展中的作用以及动脉粥样硬化中平滑肌细胞的起源。平滑肌细胞表型转换、其功能、保留胆固醇和脂蛋白的能力以及促炎和抗炎分子及细胞外基质蛋白的分泌、它们对其他细胞分泌的细胞外刺激的反应以及平滑肌细胞对动脉粥样斑块周围细胞的影响,对于深入了解动脉粥样硬化的分子基础至关重要。
动脉粥样斑块转录组研究将有助于识别参与动脉粥样硬化转变和发展的关键基因,以及发现诊断和治疗的新靶点。