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Farina A.,The Second University of Naples | Farina A.,Biomedical Proteomics Research Group | Chambery A.,The Second University of Naples | Esposito S.,The Second University of Naples | And 4 more authors.
Clinical Biochemistry | Year: 2010

Objective: The objective of this study was the construction of a reference map for aortic medial degeneration by a proteomic approach. Design and methods: A proteomic profiling of the media of human ascending aorta was performed by two-dimensional electrophoresis and MALDI-TOF mass spectrometry. Results: A reliable protocol for two-dimensional electrophoresis analysis of human aortic media proteins was developed allowing the selection and identification of 52 spots. Protein identifications revealed that the predominant vascular smooth muscle cell proteins isolated from grade 1 aortic medial degeneration (MD) included proteins involved in muscle contraction, protein folding, cytoskeletal structure and metabolic processes, and those with antioxidant or transport functions. The most populated functional classes were those related to muscle contraction and cytoskeletal proteins, including actin, calmodulin, calponin, myosin light chain, tropomyosin, vimentin, profilin and transgelin. Conclusions: The obtained aortic MD proteomic profile provides a relevant background for future studies aimed to find further specific molecular changes potentially related to the aortic MD process. © 2009 The Canadian Society of Clinical Chemists.

Fontana P.,University of Geneva | Fontana P.,Biomedical Proteomics Research Group | Zufferey A.,University of Geneva | Zufferey A.,Biomedical Proteomics Research Group | And 2 more authors.
Journal of Cardiovascular Translational Research | Year: 2014

The thromboxane (Tx) A2 pathway is a major contributor to the amplification of the initial platelet activation process. TxA2 mediates its effect through the thromboxane prostanoid (TP) receptor that is expressed not only in platelets, but also in endothelial cells, macrophages, and monocytes, and thus contributes to the development of atherosclerotic lesions. The TxA2 pathway is therefore a major target in the treatment of cardiovascular disease. Aspirin - the most widely used antiplatelet drug - is very effective at inhibiting platelet-derived TxA2 synthesis. However, aspirin's effects can be overcome by several other soluble agonists such as isoprostanes, which are aspirin-insensitive ligands of the TP receptor that are preferentially produced in diabetes mellitus. Other drugs, with either inhibitory effects on Tx synthase or antagonist effects on TP, have been developed with the hope of providing a better, more complete inhibition of the TxA2 pathway. © 2013 Springer Science+Business Media New York.

Turck N.,Biomedical Proteomics Research Group | Robin X.,Biomedical Proteomics Research Group | Robin X.,Swiss Institute of Bioinformatics | Walter N.,Biomedical Proteomics Research Group | And 8 more authors.
PLoS ONE | Year: 2012

Background: Ability to accurately determine time of stroke onset remains challenging. We hypothesized that an early biomarker characterized by a rapid increase in blood after stroke onset may help defining better the time window during which an acute stroke patient may be candidate for intravenous thrombolysis or other intravascular procedures. Methods: The blood level of 29 proteins was measured by immunoassays on a prospective cohort of stroke patients (N = 103) and controls (N = 132). Mann-Whitney U tests, ROC curves and diagnostic odds ratios were applied to evaluate their clinical performances. Results: Among the 29 molecules tested, GST-π concentration was the most significantly elevated marker in the blood of stroke patients (p<0.001). More importantly, GST-π displayed the best area under the curve (AUC, 0.79) and the best diagnostic odds ratios (10.0) for discriminating early (N = 22, <3 h of stroke onset) vs. late stroke patients (N = 81, >3 h after onset). According to goal-oriented distinct cut-offs (sensitivity(Se)-oriented: 17.7 or specificity(Sp)-oriented: 65.2 ug/L), the GST-π test obtained 91%Se/50%Sp and 50%Se/91%Sp, respectively. Moreover, GST-π showed also the highest AUC (0.83) and performances for detecting patients treated with tPA (N = 12) compared to ineligible patients (N = 103). Conclusions: This study demonstrates that GST-π can accurately predict the time of stroke onset in over 50% of early stroke patients. The GST-π test could therefore complement current guidelines for tPA administration and potentially increase the number of patients accessing thrombolysis. © 2012 Turck et al.

Fetaud-Lapierre V.,Biomedical Proteomics Research Group | Pastor C.M.,University of Geneva | Jorge-Costa M.,University of Geneva | Hochstrasser D.F.,Biomedical Proteomics Research Group | And 5 more authors.
Journal of Proteomics | Year: 2013

Acute pancreatitis is an inflammatory disease of the pancreas, which varies greatly in course and severity. Severe forms are associated with serious local and/or systemic complications, and eventually death. The pathobiology of acute pancreatitis is complex. Animal models have been developed to investigate pathobiological processes and identify factors determining disease course. We performed a time-course proteomic analysis using a rat model of severe necrotizing acute pancreatitis induced by taurocholate perfusion in the pancreatic ducts. Results showed that levels of proteins associated to a given biological process changed in a coordinated fashion after disease onset. It was possible to follow the response of a particular pathobiological process to pancreatitis induction and to compare the course of protein pathways. Proteins involved in acinar cell secretion were found to follow a different kinetics than other cellular processes. After an initial decrease, secretory pathway-associated proteins raised again at 18. h post-induction. This phenomenon coincided with a burst in the expression of pancreatitis-associated protein (REG3A), an acute phase protein produced by the exocrine pancreas, and with the decrease of classical markers of pancreatic injury, suggesting that the expression of proteins associated to the secretory pathway may be a modulating factor of pancreas injury. Biological significance: Acute pancreatitis (AP) is a complex inflammatory disease, the pathobiology of which is not yet fully understood. Various animal models, relying on different mechanisms of disease induction, have been developed in order to investigate pathobiological processes of AP. In this study, we performed a time-course proteomic analysis to investigate changes of the pancreas proteome occurring in an experimental model of AP induced by perfusion of taurocholate, a bile acid, into the pancreatic duct. This experimental model is characterized by a severe disease with pancreatic necrosis and systemic inflammation. The objectives of this study were to determine the kinetics of functionally related proteins in the early steps of the experimental disease in order to identify protein pathways playing key roles in AP pathobiology and to correlate these data with parameters classically used to assess disease severity. The present work provides for the first time an overview of protein expression in the pancreas during the course of taurocholate-induced necrotizing AP. We believe that correlation of these results with data obtained using proteomic or biochemical approaches in various experimental models of AP will help in highlighting new features, generating hypotheses and constitute therefore a strong and reliable basis for further targeted investigations. © 2013 Elsevier B.V.

Lescuyer P.,University of Geneva | Lescuyer P.,Biomedical Proteomics Research Group | Auer L.,University of Geneva | Converset V.,University of Geneva | And 5 more authors.
Clinica Chimica Acta | Year: 2012

Cerebrospinal fluid (CSF) rhinorrhea is a serious condition that may result in severe complications. Various laboratory tests, relying on the detection of CSF-specific proteins in nasal secretions, have been developed but diagnosis remains challenging. The aim of this study was to evaluate two new methods targeting either ß2-transferrin or beta-trace-protein. Rhinorrhea samples from patients suspected of CSF leakage (n=36) were analyzed using two-dimensional gel electrophoresis (2-DE) for CSF rhinorrhea diagnosis. Twelve patients with rhinorrhea strongly suggestive of a CSF leak also underwent a fluorescein test. The same cohort was retrospectively analyzed with a beta-trace protein immunoblot developed in-house (n=36) and a new commercial ß2-transferrin immunofixation assay (Sebia, Evry, France) (n=33). 2-DE was positive in 9 patients suffering from rhinorrhea following skull base fracture (n=3), post-surgery (n=4), or spontaneously (n=2). The 27 remaining cases were negative. These results were confirmed by the beta-trace protein immunoblot and ß2-transferrin immunofixation tests, except for one sample found negative with 2-DE but positive with the two other assays. Results from the three analytical methods were concordant with fluorescein tests. Beta-trace protein immunoblot and ß2-transferrin immunofixation assays are fast and reliable methods that allow detecting CSF leakage in nasal fluid with high sensitivity and specificity. © 2012 Elsevier B.V.

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