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

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Alajbegovic, AzraLund University,Lunds universitet,Molekylär kärlfysiologi,Forskargrupper vid Lunds universitet,Molecular Vascular Physiology,Lund University Research Groups (author)

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

Article/chapterEnglish2021

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Elsevier BV,2021

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LIBRIS-ID:oai:lup.lub.lu.se:b0b67487-804f-4080-a545-3348a678cf46
https://lup.lub.lu.se/record/b0b67487-804f-4080-a545-3348a678cf46URI
https://doi.org/10.1016/j.vph.2021.106837DOI

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Language:English
Summary in:English

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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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Kardiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cardiac and Cardiovascular Systems hsv//eng
Atherosclerosis
LDL receptor
Myocardin
Pinocytosis
Transdifferentiation

Added entries (persons, corporate bodies, meetings, titles ...)

Holmberg, JohanLund University,Lunds universitet,Molekylär kärlfysiologi,Forskargrupper vid Lunds universitet,Molecular Vascular Physiology,Lund University Research Groups(Swepub:lu)medk-jho (author)
Daoud, FatimaLund University,Lunds universitet,Molekylär kärlfysiologi,Forskargrupper vid Lunds universitet,Molecular Vascular Physiology,Lund University Research Groups(Swepub:lu)fa6003da (author)
Rippe, CatarinaLund University,Lunds universitet,Cellulär biomekanik,Forskargrupper vid Lunds universitet,Cellular Biomechanics,Lund University Research Groups(Swepub:lu)medk-cri (author)
Kalliokoski, GabriellaLund University,Lunds universitet,Pediatrisk nefrologi,Forskargrupper vid Lunds universitet,Pediatric Nephrology,Lund University Research Groups(Swepub:lu)ga5226ka (author)
Ekman, MariLund University,Lunds universitet,Molekylär kärlfysiologi,Forskargrupper vid Lunds universitet,Molecular Vascular Physiology,Lund University Research Groups(Swepub:lu)fkem-mpe (author)
Daudi, Sébastien (author)
Ragnarsson, SigurdurLund University,Lunds universitet,Blödningsrubbningar och akut typ-A dissektion,Forskargrupper vid Lunds universitet,Bleeding disorders and acute typ-A dissection,Lund University Research Groups(Swepub:lu)med-sdr (author)
Swärd, KarlLund University,Lunds universitet,Cellulär biomekanik,Forskargrupper vid Lunds universitet,Cellular Biomechanics,Lund University Research Groups(Swepub:lu)mphy-ksw (author)
Albinsson, SebastianLund University,Lunds universitet,Molekylär kärlfysiologi,Forskargrupper vid Lunds universitet,Molecular Vascular Physiology,Lund University Research Groups(Swepub:lu)mphy-sal (author)
Molekylär kärlfysiologiForskargrupper vid Lunds universitet (creator_code:org_t)

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In:Vascular Pharmacology: Elsevier BV1381537-1891

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By the author/editor: Alajbegovic, Azr ...; Holmberg, Johan; Daoud, Fatima; Rippe, Catarina; Kalliokoski, Gab ...; Ekman, Mari; show more...; Daudi, Sébastien; Ragnarsson, Sigu ...; Swärd, Karl; Albinsson, Sebas ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

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