Quo Vadis, Atherogenesis? Part 1. Smooth Muscle Cell Secretion – How Foe Becomes Friend in the Fight Against the Atherosclerotic Plaque

Abstract

Atherosclerosis is a chronic inflammatory disease in which exacerbation leads to myocardial infarction, stroke and/or lower limb ischemia. Phenotypic plasticity of artery smooth muscle cells (SMC) that can adapt to changes in the injured arterial microenvironment is a major determinant of atherosclerotic plaque vulnerability. Plaque instability has been associated with the ulceration or rupture of the fibrous cap composed primarily of SMC and collagen and elastin fibers, that covers the lipid core of the plaque. In this scenario, we, together with SMC, Dance round recent advances that have shed light on the relationship between inflammation, fibrosis and plaque vulnerability and stability. Specifically, we have addressed the question of how the secretory (fibrogenic) activity of SMC occurring within the plaque may become a plaque stabilizer (a friend). We describe a new paradigm shift in the cell biology of atherosclerosis that relates the inhibition of SMC matrix secretion and proliferation (the classical way for reducing plaque size) to the stimulation of these processes (the new way aimed at the plaque stabilization by increasing the thickness of its fibrous cap). Briefly, an increased secretion of matrix molecules, particularly collagen and elastin, by SMC could “shift” them from foe to friend in the fight against the vulnerable atherosclerotic plaque. Biomed Rev 2017; 28:134-138. Keywords: atherosclerotic plaque, fibrous cap, smooth muscle cells, macrophages, phenotypic modulation, matrix proteins, inflammation, fibrosis, colchicine