Proteomic characterization of human coronary thrombus in patients with ST-segment elevation acute myocardial infarction

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dc.contributor.authorAlonso-Orgaz, Sergio
dc.contributor.authorMoreno-Luna, Rafael
dc.contributor.authorLópez, Juan
dc.contributor.authorGil Dones, Félix
dc.contributor.authorPadial, Luis
dc.contributor.authorMoreu, Jose
dc.contributor.authorCuesta, Fernando de la
dc.contributor.authorBarderas, Maria
dc.date.accessioned2024-01-22T16:26:43Z
dc.date.available2024-01-22T16:26:43Z
dc.date.issued2014
dc.descriptionThis work was supported by grants from the Instituto de Salud Carlos III (FIS PI070537, PI11/02239), Fondos Feder, Redes temáticas de Investigación Cooperativa en Salud (RD12/0042/0071, RD06/0014/1015), and Fundación para la Investigación Sanitaria de Castilla-La Mancha (FISCAM PI2008-08, PI2008-28, PI2008-52). These results are lined up with the Spanish initiative on the Human Proteome Project (SpHPP). The CNIC is supported by the Spanish Ministerio de Economia y Competitividad and the Fundacion Pro-CNIC.
dc.description.abstractAbstract Acute myocardial infarction with ST-segment elevation (STEMI) initiates with intraluminal thrombosis and results in total occlusion of the coronary artery. To date, characterization of the coronary thrombus proteome in STEMI patients has not been yet accomplished. Therefore, we aimed to perform an in-depth proteomic characterization of the human coronary thrombus by means of three different approaches: 2-DE followed by mass spectrometry (MALDI MS/MS), 1-DE combined either with liquid chromatography coupled to mass spectrometry in a MALDI TOF/TOF (LC–MALDI-MS/MS), or in a LTQ-Orbitrap (LC–ESI-MS/MS). This approach allowed us to identify a total of 708 proteins in the thrombus. Expression in coronary thrombi (n = 20) of 14 proteins was verified, and the expression of fibrin and 6 cell markers (platelets, monocytes, neutrophils, eosinophils, T-cells and B-cells) quantified by selected reaction monitoring (SRM). A positive correlation of 5 proteins (fermitin homolog 3, thrombospondin-1, myosin-9, beta parvin and ras-related protein Rap-1b) with CD41 was found, pointing out the potential activation of a focal adhesion pathway within thrombus platelets. DIDO1 protein was found to correlate negatively with thrombus fibrin, and was found up-regulated in the plasma of these STEMI patients, which may constitute a starting point for further analyses in the search for biomarkers of thrombosis. Biological significance The proteomic characterization of the human coronary thrombus may contribute to a better understanding of the mechanisms involved in acute coronary syndrome, and thus pave the road for the identification of new therapeutic targets that may help addressing this and other thrombotic diseases. A novel methodology to characterize thrombus composition and expression of a sub-group of proteins is hereby described, which allowed linking protein expression with cellular and ECM matrix composition of the thrombus. Five proteins (fermitin homolog 3, thrombospondin-1, myosin-9, beta parvin and ras-related protein Rap-1b) co-express within the human coronary thrombus with CD41, pointing out the potential activation of a focal adhesion pathway within thrombus platelets during thrombus formation. Besides, the protein death-inducer obliterator 1, found to be expressed within the human coronary thrombus, has been proved to increase in the plasma of STEMI patients, which constitutes an important starting point for further analyses in the search for biomarkers of thrombosis.
dc.description.departmentDepto. de Genética, Fisiología y Microbiología
dc.description.facultyFac. de Ciencias Biológicas
dc.description.refereedTRUE
dc.description.sponsorshipInstituto de Salud Carlos III
dc.description.sponsorshipMinisterio de Economía y Competitividad (España)
dc.description.sponsorshipJunta de Comunidades de Castilla-La Mancha
dc.description.sponsorshipEuropean Commission
dc.description.statuspub
dc.identifier.citationAlonso-Orgaz, Sergio, et al. «Proteomic Characterization of Human Coronary Thrombus in Patients with ST-Segment Elevation Acute Myocardial Infarction». Journal of Proteomics, vol. 109, septiembre de 2014, pp. 368-81. https://doi.org/10.1016/j.jprot.2014.07.016.
dc.identifier.doi10.1016/j.jprot.2014.07.016
dc.identifier.issn1874-3919
dc.identifier.officialurlhttps://doi.org/10.1016/j.jprot.2014.07.016
dc.identifier.urihttps://hdl.handle.net/20.500.14352/94491
dc.journal.titleJournal of Proteomics
dc.language.isoeng
dc.page.final381
dc.page.initial368
dc.publisherElsevier
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsrestricted access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.cdu577.21
dc.subject.cdu616.12
dc.subject.cdu616.127-005.8
dc.subject.keywordHuman coronary artery
dc.subject.keywordAcute myocardial infarction
dc.subject.keywordFocal adhesion
dc.subject.keywordThrombosis
dc.subject.keywordDIDO1
dc.subject.ucmGenética
dc.subject.ucmCardiología
dc.subject.unesco2409 Genética
dc.subject.unesco3205.01 Cardiología
dc.titleProteomic characterization of human coronary thrombus in patients with ST-segment elevation acute myocardial infarction
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number109
dspace.entity.typePublication
relation.isAuthorOfPublication0827e638-921a-4475-9a48-b859587719c5
relation.isAuthorOfPublication.latestForDiscovery0827e638-921a-4475-9a48-b859587719c5
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