Role of inflammatory cytokines in genesis and treatment of atherosclerosis

Atherosclerosis demonstrates an increased rate of vascular smooth muscle cells (VSMC) plasticity characterized by switching from the differentiated contractile phenotype to a de-differentiated synthetic state. In healthy blood vessels, phenotypic switching represents a fundamental property of VSMC in maintaining vascular homeostasis. However, in atherosclerosis, it is an initial and necessary step in VSMC-derived foam cell formation. These foam cells play a decisive role in atherosclerosis progression since approximately half of all the foam cells are of VSMC origin. Our recent work showed that interferon-gamma (IFN-gamma), a primary inflammatory cytokine in progressive atherosclerosis, mediates VSMC phenotype switching exclusively through upregulating mini-tryptophanyl-tRNA synthetase (mini-TrpRS). Here, we discuss the pro-atherosclerotic implication of this phenomenon that inevitably occurs in the context of a more complex regulation mediated by IFN-gamma. An emerging therapeutic option for patients with progressive atherosclerosis is also discussed. (C) 2021 Elsevier Inc. All rights reserved.