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dc.contributor.authorAlonso-Orgaz, Sergio
dc.contributor.authorMoreno-Luna, Rafael
dc.contributor.authorLopez, Juan Antonio 
dc.contributor.authorGil-Dones, Felix
dc.contributor.authorPadial, Luis R
dc.contributor.authorMoreu, Jose
dc.contributor.authorde la Cuesta, Fernando
dc.contributor.authorBarderas, Maria G
dc.identifier.citationJ Proteomics. 2014 Sep 23;109:368-81.es_ES
dc.description.abstractAcute 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.es_ES
dc.description.sponsorshipThis 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. We would like to thank Dr. Gloria Alvarez-Llamas for her kind suggestions for the manuscript; Gemma Barroso from Proteomic Unit, Hospital Nacional de Paraplejicos, for her help and dedication to this work, as well as Veronica Moral and Ana Gallardo from the same Unit, and TamaraSastre andCarmenBermudez for their technical support.
dc.subjectAcute myocardial infarctiones_ES
dc.subjectFocal adhesiones_ES
dc.subjectHuman coronary arteryes_ES
dc.subject.meshAged es_ES
dc.subject.meshAged, 80 and over es_ES
dc.subject.meshBiomarkers es_ES
dc.subject.meshCoronary Thrombosis es_ES
dc.subject.meshFemale es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMale es_ES
dc.subject.meshMiddle Aged es_ES
dc.subject.meshMyocardial Infarction es_ES
dc.subject.meshProteome es_ES
dc.subject.meshGene Expression Regulation es_ES
dc.subject.meshProteomics es_ES
dc.titleProteomic characterization of human coronary thrombus in patients with ST-segment elevation acute myocardial infarctiones_ES
dc.typejournal articlees_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderFundación ProCNIC 
dc.contributor.funderRedes Tematicas de Investigacion Cooperativa en Salud (España)
dc.identifier.journalJournal of proteomicses_ES
dc.repisalud.orgCNICCNIC::Unidades técnicas::Proteómica / Metabolómicaes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RD12/0042/ 0071es_ES
dc.rights.accessRightsopen accesses_ES

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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
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