Control of cholesterol metabolism and plasma high-density lipoprotein levels by microRNA-144

Cristina M. Ramírez, Noemi Rotllan, Alexander V. Vlassov, Alberto Dávalos, Mu Li, Leigh Goedeke, Juan F. Aranda, Daniel Cirera-Salinas, Elisa Araldi, Alessandro Salerno, Amarylis Wanschel, Jiri Zavadil, Antonio Castrillo, Jungsu Kim, Yajaira Suárez, Carlos Fernández-Hernando

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

RATIONALE:: Foam cell formation because of excessive accumulation of cholesterol by macrophages is a pathological hallmark of atherosclerosis, the major cause of morbidity and mortality in Western societies. Liver X nuclear receptors (LXRs) regulate the expression of the adenosine triphosphate-binding cassette (ABC) transporters, including adenosine triphosphate-binding cassette transporter A1 (ABCA1) and adenosine triphosphate-binding cassette transporter G1 (ABCG1). ABCA1 and ABCG1 facilitate the efflux of cholesterol from macrophages and regulate high-density lipoprotein (HDL) biogenesis. Increasing evidence supports the role of microRNA (miRNAs) in regulating cholesterol metabolism through ABC transporters. OBJECTIVE:: We aimed to identify novel miRNAs that regulate cholesterol metabolism in macrophages stimulated with LXR agonists. METHODS AND RESULTS:: To map the miRNA expression signature of macrophages stimulated with LXR agonists, we performed an miRNA profiling microarray analysis in primary mouse peritoneal macrophages stimulated with LXR ligands. We report that LXR ligands increase miR-144 expression in macrophages and mouse livers. Overexpression of miR-144 reduces ABCA1 expression and attenuates cholesterol efflux to apolipoproteinA1 in macrophages. Delivery of miR-144 oligonucleotides to mice attenuates ABCA1 expression in the liver, reducing HDL levels. Conversely, silencing of miR-144 in mice increases the expression of ABCA1 and plasma HDL levels. Thus, miR-144 seems to regulate both macrophage cholesterol efflux and HDL biogenesis in the liver. CONCLUSIONS:: miR-144 regulates cholesterol metabolism via suppressing ABCA1 expression and modulation of miRNAs may represent a potential therapeutical intervention for treating dyslipidemia and atherosclerotic vascular disease.

Original languageEnglish (US)
Pages (from-to)1592-1601
Number of pages10
JournalCirculation Research
Volume112
Issue number12
DOIs
StatePublished - Jun 7 2013
Externally publishedYes

Fingerprint

HDL Lipoproteins
MicroRNAs
Adenosine Triphosphate
Cholesterol
Macrophages
Cytoplasmic and Nuclear Receptors
Liver
Ligands
Foam Cells
Peritoneal Macrophages
Microarray Analysis
Dyslipidemias
Vascular Diseases
Oligonucleotides
HDL Cholesterol
Atherosclerosis
Liver X Receptors
Morbidity
Mortality

Keywords

  • ABCA1
  • cardiovascular research
  • cholesterol efflux
  • cholesterol homeostatis
  • high-density lipoprotein
  • lipids and lipoprotein metabolism
  • microRNAs

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Ramírez, C. M., Rotllan, N., Vlassov, A. V., Dávalos, A., Li, M., Goedeke, L., ... Fernández-Hernando, C. (2013). Control of cholesterol metabolism and plasma high-density lipoprotein levels by microRNA-144. Circulation Research, 112(12), 1592-1601. https://doi.org/10.1161/CIRCRESAHA.112.300626

Control of cholesterol metabolism and plasma high-density lipoprotein levels by microRNA-144. / Ramírez, Cristina M.; Rotllan, Noemi; Vlassov, Alexander V.; Dávalos, Alberto; Li, Mu; Goedeke, Leigh; Aranda, Juan F.; Cirera-Salinas, Daniel; Araldi, Elisa; Salerno, Alessandro; Wanschel, Amarylis; Zavadil, Jiri; Castrillo, Antonio; Kim, Jungsu; Suárez, Yajaira; Fernández-Hernando, Carlos.

In: Circulation Research, Vol. 112, No. 12, 07.06.2013, p. 1592-1601.

Research output: Contribution to journalArticle

Ramírez, CM, Rotllan, N, Vlassov, AV, Dávalos, A, Li, M, Goedeke, L, Aranda, JF, Cirera-Salinas, D, Araldi, E, Salerno, A, Wanschel, A, Zavadil, J, Castrillo, A, Kim, J, Suárez, Y & Fernández-Hernando, C 2013, 'Control of cholesterol metabolism and plasma high-density lipoprotein levels by microRNA-144', Circulation Research, vol. 112, no. 12, pp. 1592-1601. https://doi.org/10.1161/CIRCRESAHA.112.300626
Ramírez CM, Rotllan N, Vlassov AV, Dávalos A, Li M, Goedeke L et al. Control of cholesterol metabolism and plasma high-density lipoprotein levels by microRNA-144. Circulation Research. 2013 Jun 7;112(12):1592-1601. https://doi.org/10.1161/CIRCRESAHA.112.300626
Ramírez, Cristina M. ; Rotllan, Noemi ; Vlassov, Alexander V. ; Dávalos, Alberto ; Li, Mu ; Goedeke, Leigh ; Aranda, Juan F. ; Cirera-Salinas, Daniel ; Araldi, Elisa ; Salerno, Alessandro ; Wanschel, Amarylis ; Zavadil, Jiri ; Castrillo, Antonio ; Kim, Jungsu ; Suárez, Yajaira ; Fernández-Hernando, Carlos. / Control of cholesterol metabolism and plasma high-density lipoprotein levels by microRNA-144. In: Circulation Research. 2013 ; Vol. 112, No. 12. pp. 1592-1601.
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AU - Goedeke, Leigh

AU - Aranda, Juan F.

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AU - Zavadil, Jiri

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