Heart-brain signaling in patent foramen ovale-related stroke: differential plasma proteomic expression patterns revealed with a 2-pass liquid chromatography-tandem mass spectrometry discovery workflow
| Autor: | Scott Peterman, Ignacio Inglessis-Azuaje, Eng H. Lo, Mary F. Lopez, David McMullin, Alejandra Garces, Jennifer N. Sutton, Maryann Vogelsang, Zareh Demirjian, Bryan Krastins, MingMing Ning, Igor F. Palacios, Amol Prakash, Michael Athanas, Ferdinand Buonanno, David A. Sarracino, G. William Dec, Mikaela Elia, Kathleen Feeney |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Proteomics Pathology medicine.medical_specialty Foramen Ovale Patent Bioinformatics General Biochemistry Genetics and Molecular Biology Article Cohort Studies Young Adult Text mining Tandem Mass Spectrometry medicine Humans Biomarker discovery Stroke business.industry Brain Heart General Medicine Middle Aged medicine.disease Cardiovascular physiology Gene Expression Regulation Circulatory system Patent foramen ovale Female Signal transduction business Chromatography Liquid Signal Transduction |
| Zdroj: | Journal of investigative medicine : the official publication of the American Federation for Clinical Research. 60(8) |
| ISSN: | 1708-8267 |
| Popis: | Patent foramen ovale (PFO) is highly prevalent and associated with more than 150,000 strokes per year. Traditionally, it is thought that PFOs facilitate strokes by allowing venous clots to travel directly to the brain. However, only a small portion of PFO stroke patients have a known tendency to form blood clots, and the optimal treatment for this multiorgan disease is unclear. Therefore, mapping the changes in systemic circulation of PFO-related stroke is crucial in understanding the pathophysiology to individualize the best clinical treatment for each patient. We initiated a study using a novel quantitative, 2-pass discovery workflow using high-resolution liquid chromatography–mass spectrometry/mass spectrometry coupled with label-free analysis to track protein expression in PFO patients before and after endovascular closure of the PFO. Using this approach, we were able to demonstrate quantitative differences in protein expression between both PFO-related and non–PFO-related ischemic stroke groups as well as before and after PFO closure. As an initial step in understanding the molecular landscape of PFO-related physiology, our methods have yielded biologically relevant information on the synergistic and functional redundancy of various cell-signaling molecules with respect to PFO circulatory physiology. The resulting protein expression patterns were related to canonical pathways including prothrombin activation, atherosclerosis signaling, acute-phase response, LXR/RXR activation, and coagulation system. In particular, after PFO closure, numerous proteins demonstrated reduced expression in stroke-related canonical pathways such as acute inflammatory response and coagulation signaling. These findings demonstrate the feasibility and robustness of using a proteomic approach for biomarker discovery to help gauge therapeutic efficacy in stroke. |
| Databáze: | OpenAIRE |
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