Translating the microRNA signature of microvesicles derived from human coronary artery smooth muscle cells in patients with familial hypercholesterolemia and coronary artery disease
Por:
de Gonzalo-Calvo, D, Cenario, A, Garlaschelli, K, Pellegatta, F, Vilades, D, Nasarre, L, Camino-Lopez, S, Crespo, J, Carreras, F, Leta, R, Catapano, AL, Norata, GD, Civeira, F, Llorente-Cortes, V
Publicada:
1 may 2017
Resumen:
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-qPCIt
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 mu m-1 pm 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. (C) 2017 Elsevier Ltd. All rights reserved.
Filiaciones:
de Gonzalo-Calvo, D:
Biomed Res Inst St Pau IIB St Pau, Grp Lipids & Cardiovasc Pathol, Av St Antoni Maria Claret 167, Barcelona 08025, Spain
Inst Salud Carlos III, CIBERCV, Madrid, Spain
Cenario, A:
Inst Salud Carlos III, CIBERCV, Madrid, Spain
Univ Zaragoza, Hosp Univ Miguel Servet, IIS Aragon, Lipid Unit, Zaragoza, Spain
Garlaschelli, K:
Univ Zaragoza, Hosp Univ Miguel Servet, Mol Res Lab, IIS Aragon, Zaragoza, Spain
Pellegatta, F:
Univ Zaragoza, Hosp Univ Miguel Servet, Mol Res Lab, IIS Aragon, Zaragoza, Spain
Bassini Hosp, SISA Ctr Study Atherosclerosis, Cinisello Balsamo, Italy
Vilades, D:
IRCCS MultiMed, Milan, Italy
Nasarre, L:
Biomed Res Inst St Pau IIB St Pau, Grp Lipids & Cardiovasc Pathol, Av St Antoni Maria Claret 167, Barcelona 08025, Spain
Camino-Lopez, S:
Hosp Santa Creu & Sant Pau, Cardiol Dept, Cardiac Imaging Unit, Barcelona, Spain
Crespo, J:
Hosp Santa Creu & Sant Pau, Cardiol Dept, Cardiac Imaging Unit, Barcelona, Spain
Carreras, F:
Inst Salud Carlos III, CIBERCV, Madrid, Spain
IRCCS MultiMed, Milan, Italy
Leta, R:
IRCCS MultiMed, Milan, Italy
Catapano, AL:
Bassini Hosp, SISA Ctr Study Atherosclerosis, Cinisello Balsamo, Italy
Biomed Res Inst St Pau IIB St Pau, Catalan Inst Cardiovasc Sci, Barcelona, Spain
Norata, GD:
Univ Zaragoza, Hosp Univ Miguel Servet, Mol Res Lab, IIS Aragon, Zaragoza, Spain
Biomed Res Inst St Pau IIB St Pau, Catalan Inst Cardiovasc Sci, Barcelona, Spain
Curtin Univ, Curtin Hlth Innovat Res Inst, Sch Biomed Sci, Perth, WA, Australia
Civeira, F:
Inst Salud Carlos III, CIBERCV, Madrid, Spain
Univ Zaragoza, Hosp Univ Miguel Servet, IIS Aragon, Lipid Unit, Zaragoza, Spain
Llorente-Cortes, V:
Biomed Res Inst St Pau IIB St Pau, Grp Lipids & Cardiovasc Pathol, Av St Antoni Maria Claret 167, Barcelona 08025, Spain
Inst Salud Carlos III, CIBERCV, Madrid, Spain
CSIC, Inst Biomed Res Barcelona IIBB, Barcelona, Spain
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