MRTFA overexpression promotes conversion of human coronary artery smooth muscle cells into lipid-laden foam cells

• DOI: 10.1016/j.vph.2021.106837
• Publication Date: 2021-01-29T06:35:11Z
• Authors: Azra Alajbegovic; Johan Holmberg; Fatima Daoud; Catarina Rippe; Gabriella Kalliok...; Mari Ekman; Sébastien Daudi; Sigurdur Ragnarsson; Karl Swärd; Sebastian Albinsson
• Keywords: 0301 basic medicine; Myocytes, Smooth Muscle; Vascular Remodeling; Lipid Metabolism; Coronary Vessels; Muscle, Smooth, Vascular; Up-Regulation; 03 medical and health sciences; HEK293 Cells; Receptors, LDL; Neointima; Cell Transdifferentiation; Trans-Activators; Humans; Pinocytosis; Foam Cells

Smooth muscle cells contribute significantly to lipid-laden foam cells in atherosclerotic plaques. However, the underlying mechanisms transforming smooth muscle cells into foam cells are poorly understood. The purpose of this study was to gain insight into the molecular mechanisms regulating smooth muscle foam cell formation.Using human coronary artery smooth muscle cells we found that the transcriptional co-activator MRTFA promotes lipid accumulation via several mechanisms, including direct transcriptional control of LDL receptor, enhanced fluid-phase pinocytosis and reduced lipid efflux. Inhibition of MRTF activity with CCG1423 and CCG203971 significantly reduced lipid accumulation. Furthermore, we demonstrate enhanced MRTFA expression in vascular remodeling of human vessels.This study demonstrates a novel role for MRTFA as an important regulator of lipid homeostasis in vascular smooth muscle cells. Thus, MRTFA could potentially be a new therapeutic target for inhibition of vascular lipid accumulation.