Chistiakov Dimitry A, Orekhov Alexander N, Bobryshev Yuri V
Department of Medical Nanobiotechnology, Pirogov Russian State Medical University, Moscow 117997, Russian Federation.
Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow 125315, Russian Federation.
Mini Rev Med Chem. 2018;18(7):597-608. doi: 10.2174/1389557517666170419113211.
Chemokines play a significant role in initial and advanced steps of atherogenesis. In early steps, chemokines control the adhesion of leukocytes to endothelial cells (ECs) followed by transmigration of monocytes and their deposition in the intima where they differentiate to proinflammatory macrophages. Except for proinflammatory activity, chemokines are responsible for homeostasis and homing of progenitor cells. Recently, microRNAs (miRs) were found to control expression and activity of chemokines in ECs, vascular smooth muscle cells (VSMCs), and macrophages at different steps of atherogenesis. Expression of the proatherogenic chemokine CXCL1 is suppressed by miR-181 that down-regulates nuclear transcription factor NF-kB stimulation in ECs therefore weakening the adhesiveness of the endothelium for monocytes. MiR-126 activates the endothelial production of a chemokine CXCL12 via self-multiplying feedback loop to promote re-endothelialization and support lesion stability. MiR-155 is proatherogenic by induction of the inflammatory chemokine CCL2 in macrophages. In fact, chemokines, their receptors, and relevant miRs form a complex network that exerts pro- and anti-inflammatory properties in vascular cells during different steps of atherogenic process. Obtaining new information about complicated relations between miRs and chemokines may create prerequisites for the development of novel approaches to treat atherosclerosis.
趋化因子在动脉粥样硬化的起始和进展过程中发挥着重要作用。在早期阶段，趋化因子控制白细胞与内皮细胞（ECs）的黏附，随后单核细胞迁移并沉积在内膜，在那里它们分化为促炎巨噬细胞。除了促炎活性外，趋化因子还负责祖细胞的稳态和归巢。最近发现，微小RNA（miRs）在动脉粥样硬化的不同阶段控制ECs、血管平滑肌细胞（VSMCs）和巨噬细胞中趋化因子的表达和活性。促动脉粥样硬化趋化因子CXCL1的表达受到miR-181的抑制，miR-181下调ECs中的核转录因子NF-κB刺激，从而削弱内皮对单核细胞的黏附性。miR-126通过自我增殖反馈环激活趋化因子CXCL12的内皮生成，以促进内皮再形成并维持病变稳定性。miR-155通过诱导巨噬细胞中的炎性趋化因子CCL2而具有促动脉粥样硬化作用。事实上，趋化因子、它们的受体以及相关的miRs形成了一个复杂的网络，在动脉粥样硬化过程的不同阶段对血管细胞发挥促炎和抗炎特性。获取有关miRs与趋化因子之间复杂关系的新信息可能为开发治疗动脉粥样硬化的新方法创造前提条件。
