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REVIEW: Immunotropic Effects and Proposed Mechanism of Action for 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase Inhibitors (Statins)

T. I. Arefieva1,2, A. Yu. Filatova1,a*, A. V. Potekhina1, and A. M. Shchinova1

1National Medical Research Center of Cardiology, Ministry of Health of the Russian Federation, 121552 Moscow, Russia

2Kurchatov Institute National Research Center Complex, 123182 Moscow, Russia

* To whom correspondence should be addressed.

Received November 9, 2017; Revision received March 28, 2018
Inhibitors of HMG-CoA reductase (statins) are the major group of lipid-lowering drugs. Along with hypocholesterolemic activity, statins exhibit anti-inflammatory and immunomodulatory properties that expand their clinical use, particularly, in the treatment of chronic inflammatory and autoimmune disorders. In this review, we critically analyze the data of statin effects on immune cells (e.g., monocytes and T cells) involved in the development of atherosclerosis and other chronic inflammatory diseases. We (i) discuss the properties of statins and routes of cell entry, as well as their major intracellular targets; (ii) evaluate the data on the effects of statins on the subset composition of circulatory monocytes, ability of monocytes to migrate to the site of inflammation (cell motility and expression of adhesion molecules and chemokine receptors), production of cytokines, matrix metalloproteinases, and reactive oxygen species by monocytes/macrophages, and antigen-presenting activity in peripheral blood monocyte-derived dendritic cells; and (iii) summarize the data on the regulation of proliferation and differentiation of various CD4+ T cell subsets (type 1/2/17 helper T cells and regulatory T cells) by statins.
KEY WORDS: HMG-CoA reductase inhibitors, statins, monocytes, macrophages, T cells

DOI: 10.1134/S0006297918080023