Person: Gil Dones, Félix
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First Name
Félix
Last Name
Gil Dones
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Biológicas
Department
Genética, Fisiología y Microbiología
Area
Genética
Identifiers
6 results
Search Results
Now showing 1 - 6 of 6
Item Modification of the Secretion Pattern of Proteases, Inflammatory Mediators, and Extracellular Matrix Proteins by Human Aortic Valve is Key in Severe Aortic Stenosis(Molecular and cellular proteomics, 2013) Álvarez Llamas, Gloria; Martín Rojas, Tatiana; Cuesta, Fernando De La; Calvo, Enrique; Gil Dones, Félix; Dardé, Veronica ; López Almodovar, Luis ; Padial, Luis ; Lopez, Juan Antonio; Vivanco Martínez, Fernando; Barderas, MariaOne of the major challenges in cardiovascular medicine is to identify candidate biomarker proteins. Secretome analysis is particularly relevant in this search as it focuses on a subset of proteins released by a cell or tissue under certain conditions. The sample can be considered as a plasma subproteome and it provides a more direct approximation to the in vivo situation. Degenerative aortic stenosis is the most common worldwide cause of valve replacement. Using a proteomic analysis of the secretome from aortic stenosis valves we could identify candidate markers related to this pathology, which may facilitate early diagnosis and treatment. For this purpose, we have designed a method to validate the origin of secreted proteins, demonstrating their synthesis and release by the tissue and ruling out blood origin. The nLC-MS/MS analysis showed the labeling of 61 proteins, 82% of which incorporated the label in only one group. Western blot and selective reaction monitoring differential analysis, revealed a notable role of the extracellular matrix. Variation in particular proteins such as PEDF, cystatin and clusterin emphasizes the link between aortic stenosis and atherosclerosis. In particular, certain proteins variation in secretome levels correlates well, not only with label incorporation trend (only labeled in aortic stenosis group) but, more importantly, with alterations found in plasma from an independent cohort of samples, pointing to specific candidate markers to follow up in diagnosis, prognosis, and therapeutic intervention.Item Proteomic characterization of human coronary thrombus in patients with ST-segment elevation acute myocardial infarction(Journal of Proteomics, 2014) Alonso-Orgaz, Sergio; Moreno-Luna, Rafael; López, Juan ; Gil Dones, Félix; Padial, Luis ; Moreu, Jose; Cuesta, Fernando de la; Barderas, MariaAbstract 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.Item Tissue proteomics in atherosclerosis: elucidating the molecular mechanisms of cardiovascular diseases(Expert Review of Proteomics, 2009) Cuesta, Fernando de la; Álvarez Llamas, Gloria; Gil Dones, Félix; Martin-Rojas, Tatiana; Zubiri, Irene; Pastor Vargas, Carlos; Barderas, Maria ; Vivanco Martínez, FernandoAtherosclerosis is a disease with higher levels of mortality in developed countries. Comprehension of the molecular mechanisms can yield very useful information in clinics for prevention, diagnosis and recovery monitoring. Proteomics represents an ideal methodology for this purpose, as proteins constitute the effectors of the different biological processes running during pathogenesis. To date, studies in atherosclerosis have been mainly focused on the search for plasma biomarkers. However, tissue proteomics allows going deeper into tissue secretomes, arterial layers or particular cells of interest, which, in turn, constitutes a more direct approximation to in vivo operating mechanisms. The aim of this review is to report latest advances in tissue proteomics in atherosclerosis and related diseases (e.g., aortic stenosis and ischemic injury).Item Proteomics - A Powerful Tool to Deepen the Molecular Mechanisms of Aortic Stenosis Disease(Aortic Stenosis - Etiology, Pathophysiology and Treatment, 2011) Gil Dones, Félix; Cuesta, Fernando de la; Álvarez Llamas, Gloria; Padial, Luis ; López-Almodovar, Luis ; Martin-Rojas, Tatiana; Vivanco, Fernando; Barderas, MariaItem Inside human aortic stenosis: a proteomic analysis of plasma(Journal of Proteomics, 2012) Gil Dones, Félix; Darde, Verónica ; Alonso-Orgaz, Sergio; Lopez-Almodovar, Luis ; Mourino-Alvarez, Laura; Padial, Luis ; Vivanco, Fernando; Barderas, MariaValvular aortic stenosis (AS) produces a slowly progressive obstruction in left ventricular outflow track. For this reason, aortic valve replacement is warranted when the valvular stenosis is hemodinamically significant, becoming the most common worldwide cause of aortic valve surgery. Recent epidemiologic studies have revealed an association between degenerative AS and cardiovascular risk factors for atherosclerosis, althought reducing the exposure to such factors and statin therapies both fail to delay or reverse the pathology. Hence, a deeper understanding of the pathophysiology of this disease is required to identify appropriate preventive measures. A proteomic analysis of plasma will permit to know and identify the changes in protein expression induced by AS in this tissue. Using two-dimensional difference gel electrophoresis (2D-DIGE) followed by mass spectrometry (MS), we compared the crude (not pre-fractioned) and pre-fractioned plasma from AS patients and control subjects. We sought to identify plasma proteins whose expression is modified in AS. In addition we investigated if crude plasma presented some alterations in the more abundant proteins since to date, has never been studied before. We also further investigated the link between this disease and atherosclerosis with a view to identifying new potential markers and therapeutic targets.Item Analysis of the Plasma Proteome Associated with Acute Coronary Syndrome: Does a Permanent Protein Signature Exist in the Plasma of ACS Patients?(Journal of protemoe research, 2010) Dardé, Veronica ; Cuesta, Fernando de la; Gil Dones, Félix; Álvarez Llamas, Gloria; Barderas, Maria ; Vivanco Martínez, FernandoAcute coronary syndrome (ACS) is triggered by the occlusion of a coronary artery usually due to the thrombosis caused by an atherosclerotic plaque. The identification of proteins directly involved in the pathophysiological events underlying ACS will enable more precise diagnoses and a more accurate prognosis to be determined. Accordingly, we have performed a longitudinal study of the plasma proteome in ACS patients by 2-DE and DIGE. Plasma samples from patients, healthy controls, and stable coronary artery disease (CAD) patients were immunodepleted of the six most abundant proteins, and they were analyzed in parallel at four different times: 0 (on admission) and after 4, 60, and 180 days. From a total of 1400 spot proteins analyzed, 33 proteins were differentially expressed in ACS patients when compared with control subjects/stable patients. A small group of seven proteins that appear to be altered at admission remain affected for 6 months and also in the stable CAD patients. Interestingly, the maximum number of altered proteins was observed in the stable CAD patients. Some of the proteins identified had been previously associated with ACS whereas others (such as Alpha-1-B-glycoprotein, Hakata antigen, Tetranectin, Tropomyosin 4) constitute novel proteins that are altered in this pathology.