Translating the microRNA signature of microvesicles derived from human coronary artery smooth muscle cells in patients with familial hypercholesterolemia and coronary artery disease.
To analyze the impact of atherogenic lipoproteins on the miRNA signature of microvesicles derived from human coronary artery smooth muscle cells (CASMC) and to translate these results to familial hypercholesterolemia (FH) and coronary artery disease (CAD) patients.



Conditioned media was collected after exposure of CASMC to atherogenic lipoproteins. Plasma samples were collected from two independent populations of diagnosed FH patients and matched normocholesterolemic controls (Study population 1, N=50; Study population 2, N=24) and a population of patients with suspected CAD (Study population 3, N=50). Extracellular vesicles were isolated and characterized using standard techniques. A panel of 30 miRNAs related to vascular smooth muscle cell (VSMC) (patho-)physiology was analyzed using RT-qPCR.



Atherogenic lipoproteins significantly reduced levels of miR-15b-5p, -24-3p, -29b-3p, -130a-3p, -143-3p, -146a-3p, -222-3p, -663a levels (P<0.050) in microvesicles (0.1μm-1μm in diameter) released by CASMC. Two of these miRNAs, miR-24-3p and miR-130a-3p, were reduced in circulating microvesicles from FH patients compared with normocholesterolemic controls in a pilot study (Study population 1) and in different validation studies (Study populations 1 and 2) (P<0.050). Supporting these results, plasma levels of miR-24-3p and miR-130a-3p were also downregulated in FH patients compared to controls (P<0.050). In addition, plasma levels of miR-130a-3p were inversely associated with coronary atherosclerosis in a cohort of suspected CAD patients (Study population 3) (P<0.050).



Exposure to atherogenic lipoproteins modifies the miRNA profile of CASMC-derived microvesicles and these alterations are reflected in patients with FH. Circulating miR-130a-3p emerges as a potential biomarker for coronary atherosclerosis.
Group of Lipids and Cardiovascular Pathology, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; CIBERCV, Instituto de Salud Carlos III, Madrid, Spain. Electronic address: DGonzalo@santpau.cat.
David
D
de Gonzalo-Calvo
CIBERCV, Instituto de Salud Carlos III, Madrid, Spain; Lipid Unit and Molecular Research Laboratory, IIS Aragón, Hospital Universitario Miguel Servet, Universidad de Zaragoza, Zaragoza, Spain.
Ana
A
Cenarro
SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello B, Italy.
Katia
K
Garlaschelli
SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello B, Italy; IRCCS Multimedica, Milan, Italy.
Fabio
F
Pellegatta
Cardiac Imaging Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
David
D
Vilades
Group of Lipids and Cardiovascular Pathology, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
Laura
L
Nasarre
Catalan Institute of Cardiovascular Sciences, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
Sandra
S
Camino-Lopez
Catalan Institute of Cardiovascular Sciences, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
Javier
J
Crespo
CIBERCV, Instituto de Salud Carlos III, Madrid, Spain; Cardiac Imaging Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Francesc
F
Carreras
Cardiac Imaging Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Rubén
R
Leta
IRCCS Multimedica, Milan, Italy; Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.
Alberico Luigi
AL
Catapano
SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello B, Italy; Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia.
Giuseppe Danilo
GD
Norata
CIBERCV, Instituto de Salud Carlos III, Madrid, Spain; Lipid Unit and Molecular Research Laboratory, IIS Aragón, Hospital Universitario Miguel Servet, Universidad de Zaragoza, Zaragoza, Spain.
Fernando
F
Civeira
Group of Lipids and Cardiovascular Pathology, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; CIBERCV, Instituto de Salud Carlos III, Madrid, Spain; Institute of Biomedical Research of Barcelona (IIBB) - Spanish National Research Council (CSIC), Barcelona, Spain. Electronic address: cllorente@csic-iccc.org.
Vicenta
V
Llorente-Cortes
D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D055252:Cell-Derived Microparticles; D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000235:genetics / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; C554019:MIRN130 microRNA, human; D035683:MicroRNAs
Biomarker; Coronary artery disease; Coronary artery smooth muscle cells; Familial hypercholesterolemia; MicroRNAs; Microvesicles