microRNA expression profile in human coronary smooth muscle cell-derived microparticles is a source of biomarkers

  1. David de Gonzalo-Calvo 1
  2. Ana Cenarro 2
  3. Fernando Civeira 2
  4. Vicenta Llorente-Cortes 1
  1. 1 Cardiovascular Research Center (CSIC-ICCC), Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
  2. 2 Lipid Unit and Molecular Research Laboratory, IIS Aragón, Hospital Universitario Miguel Servet, Zaragoza, Spain
Revista:
Clínica e investigación en arteriosclerosis

ISSN: 0214-9168 1578-1879

Año de publicación: 2016

Volumen: 28

Número: 4

Páginas: 167-177

Tipo: Artículo

Otras publicaciones en: Clínica e investigación en arteriosclerosis

Resumen

Introduction 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 (0.1–1 μm) 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.

Información de financiación

This work was also supported by FIS PI14/01729 from Instituto de Salud Carlos III , co-financed by the European Fund for Regional Development (E.F.R.D), Fundació Marató TV3 ( 201521 10 ), PI12/1087 from Spanish Ministry of Economy and Red de Investigación Cardiovascular (RIC) RD12/0042/0027 . DdG-C was a recipient of Sara Borrell grant from the Instituto de Salud Carlos III (CD14/00109).