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

135 Scopus citations

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

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

Fingerprint Dive into the research topics of 'Control of cholesterol metabolism and plasma high-density lipoprotein levels by microRNA-144'. Together they form a unique fingerprint.

  • Cite this

    Ramírez, C. M., Rotllan, N., Vlassov, A. V., Dávalos, A., Li, M., Goedeke, L., Aranda, J. F., 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, 112(12), 1592-1601. https://doi.org/10.1161/CIRCRESAHA.112.300626