TY - JOUR
T1 - Translating the microRNA signature of microvesicles derived from human coronary artery smooth muscle cells in patients with familial hypercholesterolemia and coronary artery disease
AU - de Gonzalo-Calvo, David
AU - Cenarro, Ana
AU - Garlaschelli, Katia
AU - Pellegatta, Fabio
AU - Vilades, David
AU - Nasarre, Laura
AU - Camino-Lopez, Sandra
AU - Crespo, Javier
AU - Carreras, Francesc
AU - Leta, Rubén
AU - Catapano, Alberico Luigi
AU - Norata, Giuseppe Danilo
AU - Civeira, Fernando
AU - Llorente-Cortes, Vicenta
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Aims: 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. Methods: 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. Results: 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 (0.1 μm–1 μm 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). Conclusions: 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.
AB - Aims: 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. Methods: 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. Results: 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 (0.1 μm–1 μm 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). Conclusions: 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.
KW - Biomarker
KW - Coronary artery disease
KW - Coronary artery smooth muscle cells
KW - Familial hypercholesterolemia
KW - MicroRNAs
KW - Microvesicles
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U2 - 10.1016/j.yjmcc.2017.03.005
DO - 10.1016/j.yjmcc.2017.03.005
M3 - Article
AN - SCOPUS:85017383633
SN - 0022-2828
VL - 106
SP - 55
EP - 67
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
ER -