Please use this identifier to cite or link to this item:
https://hdl.handle.net/10356/80432
Title: | Plasma-derived extracellular vesicles contain predictive biomarkers and potential therapeutic targets for myocardial ischemic (MI) injury | Authors: | Cheow, Esther Sok Hwee Cheng, Woo Chin Lee, Chuen Neng de Kleijn, Dominique Sorokin, Vitaly Sze, Siu Kwan |
Keywords: | Apolipoprotein Clusterin DRNTU::Science::Biological sciences |
Issue Date: | 2016 | Source: | Cheow, E. S. H., Cheng, W. C., Lee, C. N., de Kleijn, D., Sorokin, V., & Sze, S. K. (2016). Plasma-derived Extracellular Vesicles Contain Predictive Biomarkers and Potential Therapeutic Targets for Myocardial Ischemic (MI) Injury. Molecular & Cellular Proteomics, 15(8), 2628-2640. doi:10.1074/mcp.M115.055731 | Series/Report no.: | Molecular & Cellular Proteomics | Abstract: | Myocardial infarction (MI) triggers a potent inflammatory response via the release of circulatory mediators, including extracellular vesicles (EVs) by damaged cardiac cells, necessary for myocardial healing. Timely repression of inflammatory response are critical to prevent and minimize cardiac tissue injuries, nonetheless, progression in this aspect remains challenging. The ability of EVs to trigger a functional response upon delivery of carried bioactive cargos, have made them clinically attractive diagnostic biomarkers and vectors for therapeutic interventions. Using label-free quantitative proteomics approach, we compared the protein cargo of plasma EVs between patients with MI and from patients with stable angina (NMI). We report, for the first time, the proteomics profiling on 252 EV proteins that were modulated with >1.2-fold after MI. We identified six up-regulated biomarkers with potential for clinical applications; these reflected post-infarct pathways of complement activation (Complement C1q subcomponent subunit A (C1QA), 3.23-fold change, p = 0.012; Complement C5 (C5), 1.27-fold change, p = 0.087), lipoprotein metabolism (Apoliporotein D (APOD), 1.86-fold change, p = 0.033; Apolipoprotein C-III (APOCC3), 2.63-fold change, p = 0.029) and platelet activation (Platelet glycoprotein Ib alpha chain (GP1BA), 9.18-fold change, p < 0.0001; Platelet basic protein (PPBP), 4.72-fold change, p = 0.027). The data have been deposited to the ProteomeXchange with identifier PXD002950. This novel biomarker panel was validated in 43 patients using antibody-based assays (C1QA (p = 0.005); C5 (p = 0.0047), APOD (p = 0.0267); APOC3 (p = 0.0064); GP1BA (p = 0.0031); PPBP (p = 0.0465)). We further present that EV-derived fibrinogen components were paradoxically down-regulated in MI, suggesting that a compensatory mechanism may suppress post-infarct coagulation pathways, indicating potential for therapeutic targeting of this mechanism in MI. Taken together, these data demonstrated that plasma EVs contain novel diagnostic biomarkers and therapeutic targets that can be further developed for clinical use to benefit patients with coronary artery diseases (CADs). | URI: | https://hdl.handle.net/10356/80432 http://hdl.handle.net/10220/46550 |
ISSN: | 1535-9476 | DOI: | 10.1074/mcp.M115.055731 | Rights: | © 2016 American Society for Biochemistry and Molecular Biology (ASBMB). This paper was published in Molecular & Cellular Proteomics and is made available as an electronic reprint (preprint) with permission of American Society for Biochemistry and Molecular Biology (ASBMB). The published version is available at: [http://dx.doi.org/10.1074/mcp.M115.055731]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | SBS Journal Articles |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Plasma-derived Extracellular Vesicles Contain Predictive Biomarkers and Potential Therapeutic Targets for Myocardial Ischemic (MI) Injury.pdf | 2.03 MB | Adobe PDF | ![]() View/Open |
SCOPUSTM
Citations
33
Updated on Sep 2, 2020
PublonsTM
Citations
40
Updated on Jan 23, 2021
Page view(s)
177
Updated on Jan 24, 2021
Download(s) 50
45
Updated on Jan 24, 2021
Google ScholarTM
Check
Altmetric
Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.