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

Azra Alajbegovic, Johan Holmberg, Fatima Daoud, Catarina Rippe, Gabriella Kalliokoski, Mari Ekman, Sébastien Daudi, Sigurdur Ragnarsson, Karl Swärd, Sebastian Albinsson

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: 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. Approach and results: 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. Conclusions: 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.

Original languageEnglish
Article number106837
JournalVascular Pharmacology
Volume138
Early online date2021 Jan 29
DOIs
Publication statusPublished - 2021 Jun 1

Subject classification (UKÄ)

  • Cell and Molecular Biology
  • Cardiac and Cardiovascular Systems

Keywords

  • Atherosclerosis
  • LDL receptor
  • Myocardin
  • Pinocytosis
  • Transdifferentiation

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