The fibrous cap: a promising target in the pharmacotherapy of atherosclerosis

Abstract

Recent advances have shed light on the relationship between smooth muscle cell (SMC) phenotypic modulation, resolution of inflammation and atherosclerotic plaque stability. The thick fibrous cap covering the lipid core of plaques is composed of bundles of SMC and collagen fibers and few macrophages and lymphocytes, all of which make the plaque resistant to rupture. The thin fibrous cap contains many macrophages and lymphocytes, few SMC and less collagen fibers, all of which may weaken the cap, leaving the plaque vulnerable to rupture. In the present Dance Round, we, at a pharmacotherapeutic level, address the possibility of how the control over the activity of the essential cellular components of the plaque, particularly its fibrous cap, could be implicated in plaque stabilization, focusing on (i) the modulation of SMC from contractile to secretory (fibrogenic) phenotype, (ii) the control on plaque inflammation-resolution processes, and (iii) the reduction of plaque lipid content. Further studies on both unstable plaque and aortic aneurysm, which share a similar, matrix-based vulnerability, may bring new insights for pharmacotherapy of vascular injuries.