Mini-Reviews in Medicinal Chemistry, Vol 18, No 7 (2018)

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"Chemokines and Relevant microRNAs in the Atherogenic Process"

Dr. Dimitry A Chistiakov, Prof. Alexander N Orekhov, Dr. Yuri V Bobryshev


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 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 a new knowledge about complicated relations between miRs and chemokines may create prerequisites for development of novel therapeutic approaches to treat atherogenesis.


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