title: Identification of a circulating microvesicle protein network involved in ST-elevation myocardial infarction.
abstract: Membrane microvesicles (MVs) are released from activated cells, most notably platelets, into the circulation. They represent an important mode of intercellular communication, and their number is increased in patients with acute coronary syndromes. We present here a differential proteomic analysis of plasma MVs from ST-elevation myocardial infarction (STEMI) patients and stable coronary artery disease (SCAD) controls. The objective was the identification of MVs biomarkers/drug targets that could be relevant for the pathogenesis of the acute event. Proteome analysis was based on 2D-DIGE, and mass spectrometry. Validations were by western blotting in an independent cohort of patients and healthy individuals. A systems biology approach was used to predict protein-protein interactions and their relation with disease. Following gel image analysis, we detected 117 protein features that varied between STEMI and SCAD groups (fold change cut-off ≥2; p<0.01). From those, 102 were successfully identified, corresponding to 25 open-reading frames (ORFs). Most of the proteins identified are involved in inflammatory response and cardiovascular disease, with 11 ORFs related to infarction. Among others, we report an up-regulation of α2-macroglobulin isoforms, fibrinogen, and viperin in MVs from STEMI patients. Interestingly, several of the proteins identified are involved in thrombogenesis (e.g. α2-macroglobulin, and fibrinogen). In conclusion, we provide a unique panel of proteins that vary between plasma MVs from STEMI and SCAD patients and that might constitute a promising source of biomarkers/drug targets for myocardial infarction.
authors.forename: Paula
authors.initials: P
authors.lastname: Vélez
authors.forename: Andrés F
authors.initials: AF
authors.lastname: Parguiña
authors.forename: Raymundo
authors.initials: R
authors.lastname: Ocaranza-Sánchez
authors.forename: Lilian
authors.initials: L
authors.lastname: Grigorian-Shamagian
authors.forename: Isaac
authors.initials: I
authors.lastname: Rosa
authors.forename: Sergio
authors.initials: S
authors.lastname: Alonso-Orgaz
authors.forename: Fernando
authors.initials: F
authors.lastname: de la Cuesta
authors.forename: Esteban
authors.initials: E
authors.lastname: Guitián
authors.forename: José
authors.initials: J
authors.lastname: Moreu
authors.forename: María G
authors.initials: MG
authors.lastname: Barderas
authors.forename: José Ramón
authors.initials: JR
authors.lastname: González-Juanatey
authors.affiliation: Dr. Ángel García, Centro de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, Avda de Barcelona s/n, 15782 Santiago de Compostela, Spain, Tel.: +34 881 815429, Fax: +34 881 815474, E-mail: angel.garcia@usc.es.
authors.forename: Ángel
authors.initials: Á
authors.lastname: García
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005340:Fibrinogen / Q000737:chemistry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D016366:Open Reading Frames; D044925:Oxidoreductases Acting on CH-CH Group Donors; D025941:Protein Interaction Mapping; D011506:Proteins / Q000737:chemistry; D020543:Proteome; D040901:Proteomics / Q000379:methods; D049490:Systems Biology; D000511:alpha-Macroglobulins / Q000737:chemistry; D000090123:Viperin Protein
chemical_list: D015415:Biomarkers; D005340:Fibrinogen; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011506:Proteins; D020543:Proteome; D000511:alpha-Macroglobulins; C444427:RSAD2 protein, human; D000090123:Viperin Protein
keywords: Microvesicles; ST-elevation myocardial infarction; proteomics