David de Gonzalo-Calvo1, Ana Cenarro2, Katia Garlaschelli3, Fabio Pellegatta4, David Vilades5, Laura Nasarre6, Sandra Camino-Lopez7, Javier Crespo7, Francesc Carreras8, Rubén Leta5, Alberico Luigi Catapano9, Giuseppe Danilo Norata10, Fernando Civeira2, Vicenta Llorente-Cortes11. 1. 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. 2. 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. 3. SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello B, Italy. 4. SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello B, Italy; IRCCS Multimedica, Milan, Italy. 5. Cardiac Imaging Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 6. Group of Lipids and Cardiovascular Pathology, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain. 7. Catalan Institute of Cardiovascular Sciences, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain. 8. CIBERCV, Instituto de Salud Carlos III, Madrid, Spain; Cardiac Imaging Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 9. IRCCS Multimedica, Milan, Italy; Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy. 10. 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. 11. 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.
Abstract
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 (0.1μm-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). 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.
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 FHpatients 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 (0.1μm-1μm in diameter) released by CASMC. Two of these miRNAs, miR-24-3p and miR-130a-3p, were reduced in circulating microvesicles from FHpatients 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 FHpatients 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.
Authors: Rocío Toro; Sara Blasco-Turrión; Francisco José Morales-Ponce; Pablo Gonzalez; Pablo Martínez-Camblor; Amador López-Granados; Ramon Brugada; Oscar Campuzano; Alexandra Pérez-Serra; Felix Rosa Longobardo; Alipio Mangas; Vicenta Llorente-Cortes; David de Gonzalo-Calvo Journal: J Mol Med (Berl) Date: 2018-07-14 Impact factor: 4.599
Authors: Margherita A C Pomatto; Chiara Gai; Maria Chiara Deregibus; Ciro Tetta; Giovanni Camussi Journal: Int J Endocrinol Date: 2018-04-01 Impact factor: 3.257
Authors: David de Gonzalo-Calvo; Iván D Benítez; Lucía Pinilla; Amara Carratalá; Anna Moncusí-Moix; Clara Gort-Paniello; Marta Molinero; Jessica González; Gerard Torres; María Bernal; Silvia Pico; Raquel Almansa; Noelia Jorge; Alicia Ortega; Elena Bustamante-Munguira; José Manuel Gómez; Milagros González-Rivera; Dariela Micheloud; Pablo Ryan; Amalia Martinez; Luis Tamayo; César Aldecoa; Ricard Ferrer; Adrián Ceccato; Laia Fernández-Barat; Ana Motos; Jordi Riera; Rosario Menéndez; Dario Garcia-Gasulla; Oscar Peñuelas; Antoni Torres; Jesús F Bermejo-Martin; Ferran Barbé Journal: Transl Res Date: 2021-05-25 Impact factor: 7.012