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 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 Secretome analysis of atherosclerotic and non-atherosclerotic arteries reveals dynamic extracellular remodeling during pathogenesis(Journal of Proteome, 2012) Cuesta, Fernando de la; Barderas, Maria G.; Calvo, Enrique; Zubiri, Irene; Maroto, Aroa S.; Darde, Veronica M.; Martin-Rojas, Tatiana; Gil Dones, Félix; Posada-Ayala, Maria; Tejerina, Teresa; Lopez, Juan A.; Vivanco Martínez, Fernando; Alvarez-Llamas, GloriaAims: Early detection of cardiovascular diseases and knowledge of underlying mechanisms is essential. Tissue secretome studies resemble more closely to the in vivo situation, showing a much narrower protein concentrations dynamic range than plasma. This study was aimed to the analysis of human arterial tissue secretome and to the quantitative comparison of healthy and atherosclerotic secretome to discover proteins with key roles in atherosclerosis development. Methods and results: Secretomes from three biological replicates of human atherosclerotic coronary arteries (APC), preatherosclerotic coronaries (PC) and mammaries (M) were analyzed by LC-MS/MS. The identified proteins were submitted to Ingenuity Pathway Analysis (IPA) tool. Label-free MS/MS based quantification was performed and validated by immunohistochemistry. 64 proteins were identified in the 3 replicates of at least one of the 3 groups and 15 secreted proteins have not been previously reported in plasma. Four proteins were significantly released in higher amounts by mammary tissue: gelsolin, vinculin, lamin A/C and phosphoglucomutase 5. Conclusion: The study of tissue secretome reveals key proteins involved in atherosclerosis which have not been previously reported in plasma. Novel proteins are here highlighted which could be potential therapeutic targets in clinical practice. This article is part of a Special Issue entitled: Proteomics: The clinical link.Item Valvular Aortic Stenosis: A Proteomic Insight(Clinical Medicine Insights: Cardiology, 2010) Gil Dones, Félix; Martin-Rojas, Tatiana; Lopez-Almodovar, Luis ; Cuesta, Fernando de La; Darde, Veronica ; Alvarez-Llamas, Gloria; Juarez-Tosina, Rocio; Barroso, Gemma; Vivanco, Fernando; Padial, Luis ; Barderas, MariaCalcified aortic valve disease is a slowly progressive disorder that ranges from mild valve thickening with no obstruction of blood flow, known as aortic sclerosis, to severe calcification with impaired leaflet motion or aortic stenosis. In the present work we describe a rapid, reproducible and effective method to carry out proteomic analysis of stenotic human valves by conventional 2-DE and 2D-DIGE, minimizing the interference due to high calcium concentrations. Furthermore, the protocol permits the aortic stenosis proteome to be analysed, advancing our knowledge in this area. Until recently, aortic stenosis (AS) was considered a passive process secondary to calcium deposition in the aortic valves. However, it has recently been highlighted that the risk factors associated with the development of calcified AS in the elderly are similar to those of coronary artery disease. Furthermore, degenerative AS shares histological characteristics with atherosclerotic plaques, leading to the suggestion that calcified aortic valve disease is a chronic inflammatory process similar to atherosclerosis. Nevertheless, certain data does not fit with this theory making it necessary to further study this pathology. The aim of this study is to develop an effective protein extraction protocol for aortic stenosis valves such that proteomic analyses can be performed on these structures. In the present work we have defined a rapid, reproducible and effective method to extract proteins and that is compatible with 2-DE, 2D-DIGE and MS techniques. Defining the protein profile of this tissue is an important and challenging task that will help to understand the mechanisms of physiological/pathological processes in aortic stenosis valves.Item A clinical perspective on the utility of alpha 1 antichymotrypsin for the early diagnosis of calcific aortic stenosis(Clinical Proteomics, 2017) Martin-Rojas, Tatiana; Mourino-Alvarez, Laura; Gil Dones, Félix; Cuesta, Fernando de la; Rosello-Lleti, Esther; Laborde, Carlos ; Rivera, Miguel; Lopez-Almodovar, Luis Fernando; Lopez, Juan Antonio; Akerstrom, Finn ; Padial, Luis ; Barderas, MariaBackground: Calcific aortic stenosis (CAS) is the most common heart valve disease in the elderly, representing an important economic and social burden in developed countries. Currently, there is no way to predict either the onset or progression of CAS, emphasizing the need to identify useful biomarkers for this condition. Methods: We performed a multi-proteomic analysis on different kinds of samples from CAS patients and healthy donors: tissue, secretome and plasma. The results were validated in an independent cohort of subjects by immunohistochemistry, western blotting and selected reaction monitoring. Results: Alpha 1 antichymotrypsin (AACT) abundance was altered in the CAS samples, as confirmed in the validation phase. The significant changes observed in the amounts of this protein strongly suggest that it could be involved in the molecular mechanisms underlying CAS. In addition, our results suggest there is enhanced release of AACT into the extracellular fluids when the disease commences. Conclusions: The significant increase of AACT in CAS patients suggests it fulfils an important role in the physiopathology of this disease. These results permit us to propose that AACT may serve as a potential marker for the diagnosis of CAS, with considerable clinical value.Item An Optimal Protocol to Analyze the Rat Spinal Cord Proteome(Biomarker Insights, 2009) Gil Dones, Félix; Alonso-Orgaz, Sergio; Avila, Gerardo; Martin-Rojas, Tatiana; Moral-Darde, Veronica; Barroso, Gemma; Vivanco Martínez, Fernando; Scott-Taylor, Julian; Barderas, MariaSince the function of the spinal cord depends on the proteins found there, better defing the normal Spinal Cord Proteome is an important and challenging task. Although brain and cerebrospinal fluid samples from patients with different central nervous system (CNS) disorders have been studied, a thorough examination of specific spinal cord proteins and the changes induced by injury or associated to conditions such as neurodegeneration, spasticity and neuropathies has yet to be performed. In the present study, we aimed to describe total protein content in the spinal cord of healthy rats, employing different proteomics tools. Accordingly, we have developed a fast, easy, and reproducible sequential protocol for protein extraction from rat spinal cords. We employed conventional two dimensional electrophoresis (2DE) in different pH ranges (eg. 4–7, 3–11 NL) combined with identification by mass spectrometry (MALDI-TOF/TOF), as well as first dimension protein separation combined with Liquid Chromatography Mass Spectrometry/Mass Spectrometry (LC-MS/MS) to maximise the benefits of this technology. The value of these techniques is demonstrated here by the identification of several proteins known to be associated with neuroglial structures, neurotransmission, cell survival and nerve growth in the central nervous system. Furthermore this study identified many spinal proteins that have not previously been described in the literature and which may play an important role as either sensitive biomarkers of dysfunction or of recovery after Spinal Cord 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, Maria