RT Journal Article
T1 Proteomic characterization of human coronary thrombus in patients with ST-segment elevation acute myocardial infarction
A1 Alonso-Orgaz, Sergio
A1 Moreno-Luna, Rafael
A1 López, Juan
A1 Gil Dones, Félix
A1 Padial, Luis
A1 Moreu, Jose
A1 Cuesta, Fernando de la
A1 Barderas, Maria
AB 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 significanceThe 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.
PB Elsevier
SN 1874-3919
YR 2014
FD 2014
LK https://hdl.handle.net/20.500.14352/94491
UL https://hdl.handle.net/20.500.14352/94491
LA eng
NO Alonso-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.
NO This 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.
NO Instituto de Salud Carlos III
NO Ministerio de Economía y Competitividad (España)
NO Junta de Comunidades de Castilla-La Mancha
NO European Commission
DS Docta Complutense
RD 6 oct 2024