title: microRNA expression profile in human coronary smooth muscle cell-derived microparticles is a source of biomarkers.
abstract: BACKGROUND
  microRNA (miRNA) expression profile of extracellular vesicles is a potential tool for clinical practice. Despite the key role of vascular smooth muscle cells (VSMC) in cardiovascular pathology, there is limited information about the presence of miRNAs in microparticles secreted by this cell type, including human coronary artery smooth muscle cells (HCASMC). Here, we tested whether HCASMC-derived microparticles contain miRNAs and the value of these miRNAs as biomarkers.
  
  
  METHODS
  HCASMC and explants from atherosclerotic or non-atherosclerotic areas were obtained from coronary arteries of patients undergoing heart transplant. Plasma samples were collected from: normocholesterolemic controls (N=12) and familial hypercholesterolemia (FH) patients (N=12). Both groups were strictly matched for age, sex and cardiovascular risk factors. Microparticle (0.1-1μm) isolation and characterization was performed using standard techniques. VSMC-enriched miRNAs expression (miR-21-5p, -143-3p, -145-5p, -221-3p and -222-3p) was analyzed using RT-qPCR.
  
  
  RESULTS
  Total RNA isolated from HCASMC-derived microparticles contained small RNAs, including VSMC-enriched miRNAs. Exposition of HCASMC to pathophysiological conditions, such as hypercholesterolemia, induced a decrease in the expression level of miR-143-3p and miR-222-3p in microparticles, not in cells. Expression levels of miR-222-3p were lower in circulating microparticles from FH patients compared to normocholesterolemic controls. Microparticles derived from atherosclerotic plaque areas showed a decreased level of miR-143-3p and miR-222-3p compared to non-atherosclerotic areas.
  
  
  CONCLUSIONS
  We demonstrated for the first time that microparticles secreted by HCASMC contain microRNAs. Hypercholesterolemia alters the microRNA profile of HCASMC-derived microparticles. The miRNA signature of HCASMC-derived microparticles is a source of cardiovascular biomarkers.
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC), Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain. Electronic address: david.degonzalo@gmail.com.
authors.forename: David
authors.initials: D
authors.lastname: de Gonzalo-Calvo
authors.affiliation: Lipid Unit and Molecular Research Laboratory, IIS Aragón, Hospital Universitario Miguel Servet, Zaragoza, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Cenarro
authors.affiliation: Lipid Unit and Molecular Research Laboratory, IIS Aragón, Hospital Universitario Miguel Servet, Zaragoza, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Civeira
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC), Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain. Electronic address: cllorente@csic-iccc.org.
authors.forename: Vicenta
authors.initials: V
authors.lastname: Llorente-Cortes
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology*; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000473:pathology; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000503:physiopathology; D006938:Hyperlipoproteinemia Type II; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: Biomarcador; Biomarker; Cell-derived microparticles; Células de músculo liso vascular; MicroARN; MicroRNAs; Micropartículas liberadas por células; Vascular smooth muscle cell