Thromb Haemost 2014; 112(04): 716-726
DOI: 10.1160/TH14-04-0337
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Identification of a circulating microvesicle protein network involved in ST-elevation myocardial infarction

Paula Vélez
1   Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, and Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain
2   Departament of Pharmacology, Faculty of Pharmacy, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
,
Andrés F. Parguiña
1   Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, and Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain
2   Departament of Pharmacology, Faculty of Pharmacy, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
,
Raymundo Ocaranza-Sánchez
3   Cardiology Department and Coronary Unit, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
,
Lilian Grigorian-Shamagian
3   Cardiology Department and Coronary Unit, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
4   Cardiology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain
,
Isaac Rosa
1   Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, and Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain
2   Departament of Pharmacology, Faculty of Pharmacy, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
,
Sergio Alonso-Orgaz
5   Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain
,
Fernando de la Cuesta
5   Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain
,
Esteban Guitián
6   Mass Spectrometry and Proteomic Unit, Rede de Infraestructuras de Apoio á Investigación e ao Desenvolvemento Tecnolóxico (RIAIDT), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
,
José Moreu
7   Department of Cardiology, Hospital Virgen de la Salud, Toledo, Spain
,
María G. Barderas
5   Department of Vascular Physiopathology, Hospital Nacional de Parapléjicos, SESCAM, Toledo, Spain
,
José Ramón González-Juanatey
3   Cardiology Department and Coronary Unit, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
,
Ángel García
1   Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, and Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain
2   Departament of Pharmacology, Faculty of Pharmacy, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
› Institutsangaben
Financial support: This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO) [grant No. SAF2010–22151, co-funded by the European regional development fund (ERDF)]. AG acknowledges support from the Sociedad Española de Trombosis y Hemostasia – Fundación Española de Trombosis y Hemostasia (SETH-FETH). AFP is a FPI pre-doctoral fellow (MINECO). MGB was supported by grants from the Instituto de Salud Carlos III (FIS PI11/02239), Fondos Feder, Redes temáticas de Investigación Cooperativa en Salud (RD12/0042/0071). These results are lined up with the Spanish initiative on the Human Proteome Project (SpHPP).
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Publikationsverlauf

Received: 10. April 2014

Accepted after major revision: 07. Mai 2014

Publikationsdatum:
04. Dezember 2017 (online)

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Summary

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.