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

Alajbegovic, Azra LU ; Holmberg, Johan LU ; Daoud, Fatima LU ; Rippe, Catarina LU ; Kalliokoski, Gabriella LU ; Ekman, Mari LU ; Daudi, Sébastien LU ; Ragnarsson, Sigurdur LU ; Swärd, Karl LU and Albinsson, Sebastian LU (2021) In Vascular Pharmacology 138.
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... (More)

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.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Atherosclerosis, LDL receptor, Myocardin, Pinocytosis, Transdifferentiation
in
Vascular Pharmacology
volume
138
article number
106837
publisher
Elsevier
external identifiers
  • scopus:85100647586
  • pmid:33516965
ISSN
1537-1891
DOI
10.1016/j.vph.2021.106837
language
English
LU publication?
yes
id
b0b67487-804f-4080-a545-3348a678cf46
date added to LUP
2021-02-24 09:46:00
date last changed
2025-04-04 14:19:48
@article{b0b67487-804f-4080-a545-3348a678cf46,
  abstract     = {{<p>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.</p>}},
  author       = {{Alajbegovic, Azra and Holmberg, Johan and Daoud, Fatima and Rippe, Catarina and Kalliokoski, Gabriella and Ekman, Mari and Daudi, Sébastien and Ragnarsson, Sigurdur and Swärd, Karl and Albinsson, Sebastian}},
  issn         = {{1537-1891}},
  keywords     = {{Atherosclerosis; LDL receptor; Myocardin; Pinocytosis; Transdifferentiation}},
  language     = {{eng}},
  month        = {{06}},
  publisher    = {{Elsevier}},
  series       = {{Vascular Pharmacology}},
  title        = {{MRTFA overexpression promotes conversion of human coronary artery smooth muscle cells into lipid-laden foam cells}},
  url          = {{http://dx.doi.org/10.1016/j.vph.2021.106837}},
  doi          = {{10.1016/j.vph.2021.106837}},
  volume       = {{138}},
  year         = {{2021}},
}